@article{doi:10.1128/spectrum.04091-23,

title = {Development and utilization of new O_{2}-independent bioreporters},

author = {Eva Agranier and Pauline Crétin and Aurélie Joublin-Delavat and Léa Veillard and Katia Touahri and François Delavat},

url = {https://journals.asm.org/doi/abs/10.1128/spectrum.04091-23},

doi = {10.1128/spectrum.04091-23},

year  = {2024},

date = {2024-03-05},

journal = {Microbiology Spectrum},

volume = {0},

number = {0},

pages = {e04091-23},

abstract = {Fluorescent proteins are used for decades, and have allowed major discoveries in biology in a wide variety of fields, and are used in environmental as well as clinical contexts. Green fluorescent protein (GFP) and all its derivatives share a common feature: they rely on the presence of dioxygen (O2) for protein maturation and fluorescence. This dependency precludes their use in anoxic environments. Here, we constructed a series of genetic circuits allowing production of KOFP-7, an O2-independant flavin-binding fluorescent protein. We demonstrated that Escherichia coli cells producing KOFP-7 are fluorescent, both at the population and single-cell levels. Importantly, we showed that, unlike cells producing GFP, cells producing KOFP-7 are fluorescent in anoxia. Finally, we demonstrated that Vibrio diazotrophicus NS1, a facultative anaerobe, is fluorescent in the absence of O2 when KOFP-7 is produced. Altogether, the development of new genetic circuits allowing O2-independent fluorescence will open new perspective to study anaerobic processes.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Goux2023.04.11.536264,

title = {Sucrose phosphorylase from Alteromonas mediterranea: structural insight into the regioselective α-glucosylation of (+)-catechin},

author = {Marine Goux and Marie Demonceaux and Johann Hendrickx and Claude Solleux and Emilie Lormeau and Folmer Fredslund and David Tezé and Bernard Offmann and Corinne André-Miral},

url = {https://www.biorxiv.org/content/10.1101/2023.04.11.536264v2},

doi = {10.1016/j.biochi.2024.01.004},

year  = {2024},

date = {2024-01-09},

urldate = {2024-01-09},

journal = {Biochimie},

publisher = {Cold Spring Harbor Laboratory},

abstract = {Sucrose phosphorylases, through transglycosylation reactions, are interesting enzymes that can transfer regioselectively glucose from sucrose, the donor substrate, onto acceptors like flavonoids to form glycoconjugates and hence modulate their solubility and bioactivity. Here, we report for the first time the structure of sucrose phosphorylase from the marine bacteria Alteromonas mediterranea (AmSP) and its enzymatic properties. Kinetics of sucrose hydrolysis and transglucosylation capacities on (+)-catechin were investigated. Wild-type enzyme (AmSP-WT) displayed high hydrolytic activity on sucrose and was devoid of transglucosylation activity on (+)-catechin. Two variants, AmSP-Q353F and AmSP-P140D catalysed the regiospecific transglucosylation of (+)-catechin: 89 % of a novel compound (+)-catechin-4′-O-α-d-glucopyranoside (CAT-4′) for AmSP-P140D and 92 % of (+)-catechin-3′-O-α-d-glucopyranoside (CAT-3′) for AmSP-Q353F. The compound CAT-4′ was fully characterized by NMR and mass spectrometry. An explanation for this difference in regiospecificity was provided at atomic level by molecular docking simulations: AmSP-P140D was found to preferentially bind (+)-catechin in a mode that favours glucosylation on its hydroxyl group in position 4′ while the binding mode in AmSP-Q353F favoured glucosylation on its hydroxyl group in position 3’.},

keywords = {},

pubstate = {forthcoming},

tppubtype = {article}

}

@article{microorganisms12010186,

title = {Genetic Insights into Biofilm Formation by a Pathogenic Strain of Vibrio harveyi},

author = {Amandine Morot and François Delavat and Alexis Bazire and Christine Paillard and Alain Dufour and Sophie Rodrigues},

url = {https://www.mdpi.com/2076-2607/12/1/186},

doi = {10.3390/microorganisms12010186},

issn = {2076-2607},

year  = {2024},

date = {2024-01-01},

urldate = {2024-01-01},

journal = {Microorganisms},

volume = {12},

number = {1},

abstract = {The Vibrio genus includes bacteria widely distributed in aquatic habitats and the infections caused by these bacteria can affect a wide range of hosts. They are able to adhere to numerous surfaces, which can result in biofilm formation that helps maintain them in the environment. The involvement of the biofilm lifestyle in the virulence of Vibrio pathogens of aquatic organisms remains to be investigated. Vibrio harveyi ORM4 is a pathogen responsible for an outbreak in European abalone Haliotis tuberculata populations. In the present study, we used a dynamic biofilm culture technique coupled with laser scanning microscopy to characterize the biofilm formed by V. harveyi ORM4. We furthermore used RNA-seq analysis to examine the global changes in gene expression in biofilm cells compared to planktonic bacteria, and to identify biofilm- and virulence-related genes showing altered expression. A total of 1565 genes were differentially expressed, including genes associated with motility, polysaccharide synthesis, and quorum sensing. The up-regulation of 18 genes associated with the synthesis of the type III secretion system suggests that this virulence factor is induced in V. harveyi ORM4 biofilms, providing indirect evidence of a relationship between biofilm and virulence.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{prasanna_semisynthetic_2023,

title = {Semisynthetic Pneumococcal Glycoconjugate Nanovaccine},

author = {Maruthi Prasanna and Rubén Varela Calvino and Annie Lambert and Maria Arista Romero and Sylvia Pujals and François Trottein and Emilie Camberlein and Cyrille Grandjean and Noemi Csaba},

url = {https://doi.org/10.1021/acs.bioconjchem.3c00252},

doi = {10.1021/acs.bioconjchem.3c00252},

issn = {1043-1802},

year  = {2023},

date = {2023-09-01},

urldate = {2023-09-01},

journal = {Bioconjugate Chemistry},

volume = {34},

number = {9},

pages = {1563--1575},

abstract = {Pneumococcal conjugate vaccines offer an excellent safety profile and high protection against the serotypes comprised in the vaccine. However, inclusion of protein antigens fromStreptococcus pneumoniaecombined with potent adjuvants and a suitable delivery system are expected to both extend protection to serotype strains not represented in the formulation and stimulate a broader immune response, thus more effective in young children, elderly, and immunocompromised populations. Along this line, nanoparticle (NP) delivery systems can enhance the immunogenicity of antigens by protecting them from degradation and increasing their uptake by antigen-presenting cells, as well as offering co-delivery with adjuvants. We report herein the encapsulation of a semisynthetic glycoconjugate (GC) composed of a synthetic tetrasaccharide mimicking theS. pneumoniae serotype 14 capsular polysaccharide (CP14) linked to the Pneumococcal surface protein A (PsaA) using chitosan NPs (CNPs). These GC-loaded chitosan nanoparticles (GC-CNPs) were not toxic to human monocyte-derived dendritic cells (MoDCs), showed enhanced uptake, and displayed better immunostimulatory properties in comparison to the naked GC. A comparative study was carried out in mice to evaluate the immune response elicited by the glycoconjugate-administered subcutaneously (SC), where the GC-CNPs displayed 100-fold higher IgG response as compared with the group treated with nonencapsulated GC. Overall, the study demonstrates the potential of this chitosan-based nanovaccine for efficient delivery of glycoconjugate antigens.},

note = {Publisher: American Chemical Society},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{depienne_click-electrochemistry_2023,

title = {Click-electrochemistry for the rapid labeling of virus, bacteria and cell surfaces},

author = {Sébastien Depienne and Mohammed Bouzelha and Emmanuelle Courtois and Karine Pavageau and Pierre-Alban Lalys and Maia Marchand and Dimitri Alvarez-Dorta and Steven Nedellec and Laura Marín-Fernández and Cyrille Grandjean and Mohammed Boujtita and David Deniaud and Mathieu Mével and Sébastien G. Gouin},

url = {https://doi.org/10.1038/s41467-023-40534-0

https://dx.doi.org/10.26434/chemrxiv-2023-q3sd8},

doi = {10.1038/s41467-023-40534-0},

issn = {2041-1723},

year  = {2023},

date = {2023-08-01},

urldate = {2023-08-01},

journal = {Nature Communications},

volume = {14},

number = {1},

pages = {5122},

abstract = {Methods for direct covalent ligation of microorganism surfaces remain poorly reported, and mostly based on metabolic engineering for bacteria and cells functionalization. While effective, a faster method avoiding the bio-incorporation step would be highly complementary. Here, we used N-methylluminol (NML), a fully tyrosine-selective protein anchoring group after one-electron oxidation, to label the surface of viruses, living bacteria and cells. The functionalization was performed electrochemically and in situ by applying an electric potential to aqueous buffered solutions of tagged NML containing the viruses, bacteria or cells. The broad applicability of the click-electrochemistry method was explored on recombinant adeno-associated viruses (rAAV2), Escherichia coli (Gram-) and Staphyloccocus epidermidis (Gram + ) bacterial strains, and HEK293 and HeLa eukaryotic cell lines. Surface electro-conjugation was achieved in minutes to yield functionalized rAAV2 that conserved both structural integrity and infectivity properties, and living bacteria and cell lines that were still alive and able to divide.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{demonceaux2023enzymatic,

title = {Enzymatic synthesis, characterization and molecular docking of a new functionalized polyphenol: Resveratrol-3, 4’-⍺-diglucoside},

author = {Marie Demonceaux and Marine Goux and Lucia Emanueli Schimith and Michele Goulart Dos Santos and Johann Hendrickx and Bernard Offmann and Corinne André-Miral},

url = {https://www.sciencedirect.com/science/article/pii/S2211715623001959},

doi = {10.1016/j.rechem.2023.100956},

year  = {2023},

date = {2023-05-16},

urldate = {2023-05-16},

journal = {Results in Chemistry},

pages = {100956},

publisher = {Elsevier},

abstract = {Transglucosylation of resveratrol by the Q345F variant of sucrose phosphorylase from Bifidobacterium adolescentis (BaSP) was extensively studied during the last decade. Indeed, Q345F is able to catalyze the synthesis of resveratrol-3-O-⍺-D-glucoside (RES-3) with yield up to 97% using a cost-effective glucosyl donor, sucrose (Kraus et al., Chemical Communications, 53(90), 12182–12184 (2017)). Despite the fact that two further products were detectable in low amounts after glucoside synthesis, they were never identified. Here, we isolated and fully characterized one of those two minor products: resveratrol-3,4′-O-⍺-D-diglucoside (RES-3,4′). This original compound had never been described before. Using bioinformatics models, we successfully explained the formation of this diglucosylated product. Indeed, with RES-3 as acceptor substrate, Q345F is able to transfer a glucosyl moiety in position 4′-OH, what had been reported as impossible in the literature. The low yield observed is due to the steric hindrance into the catalytic site between RES-3 and residues Tyr132 and Tyr344. Nevertheless, the substrate orientation in the active site is favored by stabilizing interactions. Ring A of RES-3 bearing the diol moiety is stabilized by hydrogen bonds with residues Asp50, Arg135, Asn347 and Arg399. Hydroxyl group OH-4′ shares hydrogen bonds with the catalytic residues Asp192 and Glu232. Multiple hydrophobic contacts complete the stabilization of the substrate to favor the glucosylation at position 4′. Understanding of the mechanisms allowing the glucosylation at position 4′ of resveratrol will help the development of enzymatic tools to target and control the enzymatic synthesis of original ⍺-glucosylated polyphenols with high added value and better biodisponibility.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{violo2023site,

title = {Site-Selective Unnatural Amino Acid Incorporation at Single or Multiple Positions to Control Sugar-Protein Connectivity in Glycoconjugate Vaccine Candidates},

author = {Typhaine Violo and Annie Lambert and Aline Pillot and Mathieu Fanuel and Jessica Mac-Béar and Cédric Broussard and Cyrille Grandjean and Emilie Camberlein},

url = {https://chemistry-europe.onlinelibrary.wiley.com/doi/full/10.1002/chem.202203497},

doi = {10.1002/chem.202203497},

isbn = {1521-3765},

year  = {2023},

date = {2023-03-13},

urldate = {2023-01-01},

journal = {Chemistry--A European Journal},

volume = {29},

number = {15},

pages = {e202203497},

publisher = {Wiley Online Library},

abstract = {In cellulo site-specific unnatural amino acid incorporation based on amber stop codon reassignment is a powerful tool to modify proteins at defined positions. This technique is herein applied to the selective functionalization of the Pneumococcal surface adhesin A protein at three distinct positions. Nϵ-propargyloxycarbonyl-l-lysine residues were incorporated and their alkyne groups reacted using click-chemistry with a synthetic azido-functionalized tetrasaccharide representative of one repeat unit of the Streptococcus pneumoniae serotype 14 capsular polysaccharide. Anti-PsaA antibody response induced in mice by the trivalent glycoconjugate was determined in comparison with corresponding monovalent and randomly functionalized conjugates. Our results suggest that controlled was superior to random conjugation for preserving antigenicity. In definitive, the reported strategy offers a unique opportunity to study the impact of carbohydrate antigen-carrier protein connectivity on immunogenicity.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{demonceaux2023regioselective,

title = {Regioselective glucosylation of (+)-catechin using a new variant of sucrose phosphorylase from Bifidobacterium adolescentis},

author = {Marie Demonceaux and Marine Goux and Johann Hendrickx and Claude Solleux and Frédéric Cadet and Émilie Lormeau and Bernard Offmann and Corinne André-Miral},

doi = {10.1039/D3OB00191A},

year  = {2023},

date = {2023-02-22},

urldate = {2023-02-22},

journal = {Organic & Biomolecular Chemistry},

volume = {21},

number = {11},

pages = {2307--2311},

publisher = {Royal Society of Chemistry},

abstract = {Mutation Q345F in sucrose phosphorylase from Bifidobacterium adolescentis (BaSP) has shown to allow efficient (+)-catechin glucosylation yielding a regioisomeric mixture: (+)-catechin-3′-O-α-D-glucopyranoside, (+)-catechin-5-O-α-D-glucopyranoside and (+)-catechin-3′,5-O-α-D-diglucopyranoside with a ratio of 51 : 25 : 24. Here, we efficiently increased the control of (+)-catechin glucosylation regioselectivity with a new variant Q345F/P134D. The same products were obtained with a ratio of 82 : 9 : 9. Thanks to bioinformatics models, we successfully explained the glucosylation favoured at the OH-3′ position due to the mutation P134D.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{SAUMONNEAU2023101335,

title = {Disruption of Botryococcus braunii colonies by glycoside hydrolases},

author = {Amélie Saumonneau and Nathan Lagneau and Lydia Awuor Ogonda and Catherine Dupré and Stéphanie Dutertre and Dominique Grizeau and Charles Tellier and Cyrille Grandjean and Franck Daligault},

url = {https://www.sciencedirect.com/science/article/pii/S2589014X23000063},

doi = {10.1016/j.biteb.2023.101335},

issn = {2589-014X},

year  = {2023},

date = {2023-01-13},

urldate = {2023-01-01},

journal = {Bioresource Technology Reports},

volume = {21},

pages = {101335},

abstract = {Microalgae are a promising alternative resource to fossil-based products. Botryococcus braunii is a colonial green microalga having the ability to convert CO2 by photosynthesis into long chain hydrocarbons. These are excreted and trapped in an extracellular matrix (ECM). A panel of glycosidases ranging from arabinanase, galactananase to endoglucanase was tested for their ability to lyse the polysaccharides maintaining the B. braunii colony integrity in order to release the hydrocarbons present in the extracellular matrix without harming the cells. The BpGH9 endoglucanase from Bacillus pumilus was fused with CtCBM3a from Clostridium thermocellum and yellow fluorescent protein to probe the presence of microcrystalline cellulose in the cell wall of B. braunii and to increase the efficacy of the endoglucanase. All the tested enzymes were able to some extent to dissociate the cells from the extracellular matrix while keeping them alive, suggesting the feasibility of a semi-continuous in situ recovery of hydrocarbons.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{<LineBreak>doi:10.1073/pnas.2305195120,

title = {Cooperation and cheating orchestrate Vibrio assemblages and polymicrobial synergy in oysters infected with OsHV-1 virus},

author = {Daniel Oyanedel and Arnaud Lagorce and Maxime Bruto and Philippe Haffner and Amandine Morot and Yannick Labreuche and Yann Dorant and Sébastien La Forest Divonne and François Delavat and Nicolas Inguimbert and Caroline Montagnani and Benjamin Morga and Eve Toulza and Cristian Chaparro and Jean-Michel Escoubas and Yannick Gueguen and Jeremie Vidal-Dupiol and Julien Lorgeril and Bruno Petton and Lionel Degremont and Delphine Tourbiez and Léa-Lou Pimparé and Marc Leroy and Océane Romatif and Juliette Pouzadoux and Guillaume Mitta and Frédérique Le Roux and Guillaume M. Charrière and Marie-Agnès Travers and Delphine Destoumieux-Garzón},

url = {https://www.pnas.org/doi/abs/10.1073/pnas.2305195120

https://www.biorxiv.org/content/early/2023/02/11/2023.02.11.528104},

doi = {10.1073/pnas.2305195120},

year  = {2023},

date = {2023-01-01},

urldate = {2023-01-01},

journal = {Proceedings of the National Academy of Sciences},

volume = {120},

number = {40},

pages = {e2305195120},

abstract = {Polymicrobial infections threaten the health of humans and animals but remain understudied in natural systems. We recently described the Pacific Oyster Mortality Syndrome (POMS), a polymicrobial disease affecting oyster production worldwide. In the French Atlantic coast, the disease involves coinfection with ostreid herpesvirus 1 (OsHV-1) and virulent Vibrio. However, it is unknown whether consistent Vibrio populations are associated with POMS in different regions, how Vibrio contribute to POMS, and how they interact with OsHV-1 during pathogenesis. By connecting field-based approaches in a Mediterranean ecosystem, laboratory infection assays and functional genomics, we uncovered a web of interdependencies that shape the structure and function of the POMS pathobiota. We show that Vibrio harveyi and Vibrio rotiferianus are predominant in OsHV-1-diseased oysters and that OsHV-1 drives the partition of the Vibrio community observed in the field. However only V. harveyi synergizes with OsHV-1 by promoting mutual growth and accelerating oyster death. V. harveyi shows high-virulence potential and dampens oyster cellular defenses through a type 3 secretion system, making oysters a more favorable niche for microbe colonization. In addition, V. harveyi produces a key siderophore called vibrioferrin. This important resource promotes the growth of V. rotiferianus, which cooccurs with V. harveyi in diseased oysters, and behaves as a cheater by benefiting from V. harveyi metabolite sharing. Our data show that cooperative behaviors contribute to synergy between bacterial and viral coinfecting partners. Additional cheating behaviors further shape the polymicrobial consortium. Controlling cooperative behaviors or countering their effects opens avenues for mitigating polymicrobial diseases.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{joublindelavat_genetic_2022,

title = {Genetic and physiological insights into the diazotrophic activity of a non-cyanobacterial marine diazotroph},

author = {Aurélie Joublin-Delavat and Katia Touahri and Pauline Crétin and Amandine Morot and Sophie Rodrigues and Bruno Jesus and Florian Trigodet and François Delavat},

url = {https://onlinelibrary.wiley.com/doi/10.1111/1462-2920.16261},

doi = {10.1111/1462-2920.16261},

issn = {1462-2912, 1462-2920},

year  = {2022},

date = {2022-12-01},

urldate = {2022-12-01},

journal = {Environmental Microbiology},

volume = {24},

number = {12},

pages = {6510--6523},

abstract = {Nitrogen (N2) fixation, or diazotrophy, supports a large part of primary production in oceans. Culture-independent approaches highlighted the presence in abundance of marine non-cyanobacterial diazotrophs (NCD), but their ecophysiology remains elusive, mostly because of the low number of isolated NCD and because of the lack of available genetic tools for these isolates. Here, a dual genetic and functional approach allowed unveiling the ecophysiology of a marine NCD affiliated to the species Vibrio diazotrophicus. Physiological characterization of the first marine NCD mutant obtained so far was performed using a soft-gellan assay, demonstrating that a ΔnifH mutant is not able to grow in nitrogen-free media. Furthermore, we demonstrated that V. diazotrophicus produces a thick biofilm under diazotrophic conditions, suggesting biofilm production as an adaptive response of this NCD to cope with the inhibition of nitrogen fixation by molecular oxygen. Finally, the genomic signature of V. diazotrophicus is essentially absent from metagenomic data of Tara Ocean expeditions, despite having been isolated from various marine environments. We think that the genetically tractable V. diazotrophicus strain used in this study may serve as an ideal model to study the ecophysiology of these overlooked procaryotic group.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{schimith2022polydatin,

title = {Polydatin as a therapeutic alternative for central nervous system disorders: A systematic review of animal studies},

author = {Lucia E Schimith and Michele G Dos Santos and Bruno D Arbo and Corinne André-Miral and Ana L Muccillo-Baisch and Mariana A Hort},

url = {https://onlinelibrary.wiley.com/doi/10.1002/ptr.7497},

doi = {10.1002/ptr.7497},

year  = {2022},

date = {2022-05-25},

urldate = {2022-05-25},

journal = {Phytotherapy Research},

volume = {36},

number = {7},

pages = {2852--2877},

publisher = {Wiley Online Library},

abstract = {Polydatin, or piceid, is a natural stilbene found in grapes, peanuts, and wines. Polydatin presents pharmacological activities, including neuroprotective properties, exerting preventive and/or therapeutic effects in central nervous system (CNS) disorders. In the present study, we summarize and discuss the neuroprotective effects of polydatin in CNS disorders and related pathological conditions in preclinical animal studies. A systematic review was performed by searching online databases, returning a total of 110 records, where 27 articles were selected and discussed here. The included studies showed neuroprotective effects of polydatin in experimental models of neurological disorders, including cerebrovascular disorders, Parkinson's disease, traumatic brain injuries, diabetic neuropathy, glioblastoma, and neurotoxicity induced by chemical agents. Most studies were focused on stroke (22.2%) and conducted in male rodents. The intervention protocol with polydatin was mainly acute (66.7%), with postdamage induction treatment being the most commonly used regimen (55.2%). Overall, polydatin ameliorated behavioral dysfunctions and/or promoted neurological function by virtue of its antioxidant and antiinflammatory properties. In summary, this review offers important scientific evidence for the neuroprotective effects and distinct pharmacological mechanisms of polydatin that not only enhances the present understanding but is also useful for the development of future preclinical and clinical investigations.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{dos2022neuroprotective,

title = {Neuroprotective effects of resveratrol in in vivo and in vitro experimental models of Parkinson’s disease: A systematic review},

author = {Michele Goulart Dos Santos and Lucia Emanueli Schimith and Corinne André-Miral and Ana Luiza Muccillo-Baisch and Bruno Dutra Arbo and Mariana Appel Hort},

editor = {Springer},

doi = {10.1007/s12640-021-00450-x},

year  = {2022},

date = {2022-01-12},

urldate = {2022-01-12},

journal = {Neurotoxicity Research},

pages = {1--27},

publisher = {Springer},

abstract = {Parkinson’s disease (PD) is currently the second most common neurodegenerative disease, being characterized by motor and non-motor symptoms. The therapeutic options available for its treatment are limited, do not slow the progression of the disease, and have serious side effects. For this reason, many studies have sought to find compounds with neuroprotective properties that bring additional benefits to current therapy. In this context, resveratrol is a phenolic compound, found in many plant species, capable of crossing the blood–brain barrier and having multiple biological properties. Experimental studies in vitro and in vivo have shown that it can prevent or slow the progression of a variety of diseases, including PD. In this systematic review, we summarize the effects of resveratrol in experimental in vivo and in vitro models of PD and discuss the molecular mechanisms involved in its action. The bibliographic search was performed in the databases of PubMed, Web of Science, SciELO, and Google Scholar, and based on the inclusion criteria, 41 articles were selected and discussed. Most of the included studies have demonstrated neuroprotective effects of resveratrol. In general, resveratrol prevented behavioral and/or neurological disorders, improved antioxidant defenses, reduced neuroinflammatory processes, and inhibited apoptosis. In summary, this systematic review offers important scientific evidence of neuroprotective effects of resveratrol in PD and also provide valuable information about its mechanism of action that can support future clinical studies.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{cabezas2021modulation,

title = {Modulation of the Activity and Regioselectivity of a Glycosidase: Development of a Convenient Tool for the Synthesis of Specific Disaccharides},

author = {Yari Cabezas-Pérusse and Franck Daligault and Vincent Ferrières and Olivier Tasseau and Sylvain Tranchimand},

url = {https://www.mdpi.com/1420-3049/26/18/5445},

doi = {10.3390/molecules26185445},

year  = {2021},

date = {2021-09-07},

urldate = {2021-09-07},

journal = {Molecules},

volume = {26},

number = {18},

pages = {5445},

publisher = {MDPI},

abstract = {The synthesis of disaccharides, particularly those containing hexofuranoside rings, requires a large number of steps by classical chemical means. The use of glycosidases can be an alternative to limit the number of steps, as they catalyze the formation of controlled glycosidic bonds starting from simple and easy to access building blocks; the main drawbacks are the yields, due to the balance between the hydrolysis and transglycosylation of these enzymes, and the enzyme-dependent regioselectivity. To improve the yield of the synthesis of β-d-galactofuranosyl-(1→X)-d-mannopyranosides catalyzed by an arabinofuranosidase, in this study we developed a strategy to mutate, then screen the catalyst, followed by a tailored molecular modeling methodology to rationalize the effects of the identified mutations. Two mutants with a 2.3 to 3.8-fold increase in transglycosylation yield were obtained, and in addition their accumulated regioisomer kinetic profiles were very different from the wild-type enzyme. Those differences were studied in silico by docking and molecular dynamics, and the methodology revealed a good predictive quality in regards with the regioisomer profiles, which is in good agreement with the experimental transglycosylation kinetics. So, by engineering CtAraf51, new biocatalysts were enabled to obtain the attractive central motif from the Leishmania lipophosphoglycan core with a higher yield and regioselectivity.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{robla_chitosan-based_2021,

title = {A chitosan-based nanosystem as pneumococcal vaccine delivery platform},

author = {Sandra Robla and Maruthi Prasanna and Rubén Varela-Calviño and Cyrille Grandjean and Noemi Csaba},

url = {https://doi.org/10.1007/s13346-021-00928-3},

doi = {10.1007/s13346-021-00928-3},

issn = {2190-3948},

year  = {2021},

date = {2021-04-01},

urldate = {2021-06-16},

journal = {Drug Delivery and Translational Research},

volume = {11},

number = {2},

pages = {581--597},

abstract = {Chitosan-based nanosystems have been described as interesting tools for antigen delivery and for enhancing the immunogenicity of nasally administered vaccines. As a possible vaccine delivery method, the chemical conjugation of chitosan nanocapsules with the Streptococcus pneumoniae cell membrane protein PsaA (pneumococcal surface adhesin A) is suggested here. The antigen PsaA, common to all pneumococcus serotypes, is expected to improve its uptake by immune cells and to activate specific T cells, generating an adaptive immune response against pneumococcus. With this aim, chitosan nanocapsules with thiol-maleimide conjugation between the polymer (chitosan) and the antigen (PsaA) were designed to enable the surface presentation of PsaA for immune cell recognition. Spherical-shaped particles, with a size of 266 ± 32 nm, positive charge of +30 ± 1 mV, and good stability profiles in simulated nasal fluids (up to 24 h) were achieved. PsaA association rates were three times higher compared with nanocapsules without covalent polymer-protein conjugation. Cytotoxicity studies in cell culture media showed non-toxic effect under 150 µg/mL concentration of nanocapsules, and subsequent studies on the maturation of immature dendritic cells in the presence of antigen-conjugated nanocapsules displayed peripheral blood mononuclear cell activation and lymphocyte differentiation after their presentation by dendritic cells. Secretion of TNFα following exposure to nanocapsules and the ability of nanocapsules to activate CD4 and CD8 T lymphocytes had also been studied.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{https://doi.org/10.1002/chem.202004672,

title = {Polyvalent Transition-State Analogues of Sialyl Substrates Strongly Inhibit Bacterial Sialidases**},

author = {Coralie Assailly and Clarisse Bridot and Amélie Saumonneau and Paul Lottin and Benoit Roubinet and Eva-Maria Krammer and Francesca François and Federica Vena and Ludovic Landemarre and Dimitri Alvarez Dorta and David Deniaud and Cyrille Grandjean and Charles Tellier and Sagrario Pascual and Véronique Montembault and Laurent Fontaine and Franck Daligault and Julie Bouckaert and Sébastien G Gouin},

url = {https://chemistry-europe.onlinelibrary.wiley.com/doi/abs/10.1002/chem.202004672},

doi = {https://doi.org/10.1002/chem.202004672},

year  = {2021},

date = {2021-01-01},

journal = {Chemistry – A European Journal},

volume = {27},

number = {9},

pages = {3142-3150},

abstract = {Abstract Bacterial sialidases (SA) are validated drug targets expressed by common human pathogens such as Streptococcus pneumoniae, Vibrio cholerae, or Clostridium perfringens. Noncovalent inhibitors of bacterial SA capable of reaching the submicromolar level are rarely reported. In this work, multi- and polyvalent compounds are developed, based on the transition-state analogue 2-deoxy-2,3-didehydro-N-acetylneuraminic (DANA). Poly-DANA inhibits the catalytic activity of SA from S. pneumoniae (NanA) and the symbiotic microorganism B. thetaiotaomicron (BtSA) at the picomolar and low nanomolar levels (expressed in moles of molecules and of DANA, respectively). Each DANA grafted to the polymer surpasses the inhibitory potential of the monovalent analogue by more than four orders of magnitude, which represents the highest multivalent effect reported so far for an enzyme inhibition. The synergistic interaction is shown to operate exclusively in the catalytic domain, and not in the flanked carbohydrate-binding module (CBM). These results offer interesting perspectives for the multivalent inhibition of other SA families lacking a CBM, such as viral, parasitic, or human SA.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{ogondacharacterization,

title = {Characterization and engineering of two new GH9 and GH48 cellulases from a Bacillus pumilus isolated from Lake Bogoria},

author = {Lydia A Ogonda and Amélie Saumonneau and Michel Dion and Edward K Muge and Benson M Wamalwa and Francis J Mulaa and Charles Tellier},

doi = {10.1007/s10529-020-03056-z},

year  = {2021},

date = {2021-01-01},

journal = {Biotechnology Letters},

volume = {43},

pages = {691–700},

publisher = {Springer},

abstract = {Objectives. To search for new alkaliphilic cellulases and to improve their efficiency on crystalline cellulose through molecular engineering 

Results. Two novel cellulases, BpGH9 and BpGH48, from a Bacillus pumilus strain were identified, cloned and biochemically characterized. BpGH9 is a modular endocellulase belonging to the glycoside hydrolase 9 family (GH9), which contains a catalytic module (GH) and a carbohydrate-binding module belonging to class 3 and subclass c (CBM3c). This enzyme is extremely tolerant to high alkali pH and remains significantly active at pH 10. BpGH48 is an exocellulase, belonging to the glycoside hydrolase 48 family (GH48) and acts on the reducing end of oligo-β1,4 glucanes. A truncated form of BpGH9 and a chimeric fusion with an additional CBM3a module was constructed. The deletion of the CBM3c module results in a significant decline in the catalytic activity. However, fusion of CBM3a, although in a non native position, enhanced the activity of BpGH9 on crystalline cellulose. 

 Conclusions. A new alkaliphilic endocellulase BpGH9, was cloned and engineered as a fusion protein (CBM3a-BpGH9), which led to an improved activity on crystalline cellulose.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{prasanna_use_2021,

title = {On the use of adenovirus dodecahedron as a carrier for glycoconjugate vaccines},

author = {Maruthi Prasanna and Malgorzata Podsiadla-Bialoskorska and Damian Mielecki and Nicolas Ruffier and Amina Fateh and Annie Lambert and Mathieu Fanuel and Emilie Camberlein and Ewa Szolajska and Cyrille Grandjean},

url = {https://doi.org/10.1007/s10719-021-09999-3},

doi = {10.1007/s10719-021-09999-3},

issn = {1573-4986},

year  = {2021},

date = {2021-01-01},

urldate = {2021-06-16},

journal = {Glycoconjugate Journal},

abstract = {Virus-Like Particles (VLPs) have been used as immunogenic molecules in numerous recombinant vaccines. VLPs can also serve as vaccine platform to exogenous antigens, usually peptides incorporated within the protein sequences which compose the VLPs or conjugated to them. We herein described the conjugation of a synthetic tetrasaccharide mimicking the Streptococcus pneumoniae serotype 14 capsular polysaccharide to recombinant adenoviral type 3 dodecahedron, formed by the self-assembling of twelve penton bases and investigated the induced immune response when administered subcutaneously (s.c.). Whether formulated in the form of a dodecahedron or disassembled, the glycoconjugate induced an anti-protein response after two and three immunizations equivalent to that observed when the native dodecahedron was administered. On the other hand, the glycoconjugate induced a weak anti-IgM response which diminishes after two doses but no IgM-to-IgG switch was observed in mice against the serotype 14 capsular polysaccharide. In definitive, the whole conjugation process preserved both particulate nature and immunogenicity of the adenoviral dodecahedron. Further studies are needed to fully exploit adenoviral dodecahedron potential in terms of plasticity towards sequence engineering and of its capacity to stimulate the immune system via the intranasal route of administration as well as to shift the response to the carbohydrate antigen by playing both with the carbohydrate to protein ratio and the length of the synthetic carbohydrate antigen.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Dussouy2020,

title = {Linear triazole-linked pseudo oligogalactosides as scaffolds for galectin inhibitor development.},

author = {Christophe Dussouy and Chandan Kishor and Annie Lambert and Clément Lamoureux and Helen Blanchard and Cyrille Grandjean},

doi = {10.1111/cbdd.13683},

issn = {1747-0285 (Electronic)},

year  = {2020},

date = {2020-03-01},

journal = {Chemical biology & drug design},

abstract = {Galectins play key roles in numerous biological processes. Their mode of action depends on their localization which can be extracellular, cytoplasmic or nuclear, and is partly mediated through interactions with β-galactose containing glycans. Galectins have emerged as novel therapeutic targets notably for the treatment of inflammatory disorders and cancers. This has stimulated the design of carbohydrate-based inhibitors targeting the carbohydrate recognition domains (CRDs) of the galectins. Pursuing this approach, we reasoned that linear oligo-galactosides obtained by straightforward iterative click-chemistry could mimic poly-lactosamine motifs expressed at eukaryote cell surfaces which the extracellular form of galectin-3, a prominent member of the galectin family, specifically recognizes. Affinities towards galectin-3 consistently increased with the length of the representative oligogalactosides but without reaching that of oligo-lactosamines. Elucidation of the X-ray crystal structures of the galectin-3 CRD in complex with a synthesized di- and tri-galactoside confirmed that the compounds bind within the carbohydrate-binding site. The atomic structures revealed that binding interactions mainly occur with the galactose moiety at the non-reducing end, primarily with subsites C and D of the CRD, differing from oligo-lactosamine which bind more consistently across the whole groove formed by the five subsites (A-E) of the galectin-3 CRD.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Storozhylova2020,

title = {An In Situ Hyaluronic Acid-Fibrin Hydrogel Containing Drug-Loaded Nanocapsules for Intra-Articular Treatment of Inflammatory Joint Diseases},

author = {Nataliya Storozhylova and José Crecente-Campo and David Cabaleiro and Luis Lugo and Christophe Dussouy and Sandra Sim{õ}es and Madalena Monteiro and Cyrille Grandjean and María J Alonso},

doi = {10.1007/s40883-020-00154-2},

issn = {23644141},

year  = {2020},

date = {2020-01-01},

journal = {Regenerative Engineering and Translational Medicine},

volume = {6},

number = {2},

pages = {201--216},

publisher = {Regenerative Engineering and Translational Medicine},

abstract = {Abstract: Intra-articular (IA) administration of drugs is an appealing route for the effective treatment of large-joint diseases. However, a key limitation of this route is the premature elimination of the injected drugs from the synovial cavity. The objective of this work was to develop an easily injectable controlled release system intended to prolong the activity of anti-inflammatory drugs in the articular cavity. The system was an in situ forming hydrogel, made of fibrin and hyaluronic acid (HA), loaded with nanocapsules (NCs). The NCs, consisting of an olive oil core surrounded by a HA shell, were loaded with two different drugs, dexamethasone (DMX) and a galectin-3 inhibitor. They presented a particle size in the range of 122–135 nm and a surface charge of − 29/− 31 mV. The gelation time, rheological properties and porosity of the system could be adjusted by different parameters, such as addition of fibrin crosslinkers factor XIII and α2-antiplasmin. The non-crosslinked HA-fibrin hydrogels containing 30% (v/v) NCs showed the capacity to control the release of the encapsulated drug, DMX, for 72 h in simulated synovial fluid. The preliminary in vivo evaluation of the system containing a galectin-3 inhibitor in an acute synovitis rat model showed a suppression of inflammation after IA administration compared with the non-treated control. In brief, this work shows the possibility to combine an in situ forming hydrogel and NCs as a drug delivery strategy for IA administration and suggests its potential for the treatment of arthropathies. Lay Summary: This work describes the development and characterization of a new in situ forming hydrogel adapted for intra-articular administration of anti-inflammatory drugs. The prolonged local delivery of these drugs is expected to improve the treatment of large-joint arthropathies. To achieve this objective, the hydrogel, made of biodegradable materials, was loaded with nanodeposits of drugs, named nanocapsules. The efficacy of the system, containing a new galectin-3 inhibitor as a drug candidate, was tested in a rat model of acute synovial inflammation. These results represent the first insights on the in vivo activity of a new galectin-3 inhibitor on a potential galectin-3 immunotherapeutic target for inflammatory joints diseases. [Figure not available: see fulltext.]},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Teze2020,

title = {A Single Point Mutation Converts GH84 O-GlcNAc Hydrolases into Phosphorylases: Experimental and Theoretical Evidence},

author = {David Teze and Joan Coines and Lluís Raich and Valentina Kalichuk and Claude Solleux and Charles Tellier and Corinne André-Miral and Birte Svensson and Carme Rovira},

doi = {10.1021/jacs.9b09655},

issn = {15205126},

year  = {2020},

date = {2020-01-01},

journal = {Journal of the American Chemical Society},

volume = {142},

number = {5},

pages = {2120--2124},

abstract = {Glycoside hydrolases and phosphorylases are two major classes of enzymes responsible for the cleavage of glycosidic bonds. Here we show that two GH84 O-GlcNAcase enzymes can be converted to efficient phosphorylases by a single point mutation. Noteworthy, the mutated enzymes are over 10-fold more active than naturally occurring glucosaminide phosphorylases. We rationalize this novel transformation using molecular dynamics and QM/MM metadynamics methods, showing that the mutation changes the electrostatic potential at the active site and reduces the energy barrier for phosphorolysis by 10 kcaltextperiodcenteredmol-1. In addition, the simulations unambiguously reveal the nature of the intermediate as a glucose oxazolinium ion, clarifying the debate on the nature of such a reaction intermediate in glycoside hydrolases operating via substrate-assisted catalysis.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{violo:hal-02990572,

title = {Homogenous Glycoconjugate Produced by Combined Unnatural Amino Acid Incorporation and Click-Chemistry for Vaccine Purposes},

author = {Typhaine Violo and Christophe Dussouy and Charles Tellier and Cyrille Grandjean and Emilie Camberlein},

url = {https://hal.archives-ouvertes.fr/hal-02990572},

doi = {10.3791/60821},

year  = {2020},

date = {2020-01-01},

journal = {Journal of visualized experiments : JoVE},

publisher = {JoVE},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Visnapuu2020,

title = {Identification and characterization of a β-n-acetylhexosaminidase with a biosynthetic activity from the marine bacterium paraglaciecola hydrolytica S66T},

author = {Triinu Visnapuu and David Teze and Christian Kjeldsen and Aleksander Lie and Jens Øllgaard Duus and Corinne André-Miral and Lars Haastrup Pedersen and Peter Stougaard and Birte Svensson},

doi = {10.3390/ijms21020417},

issn = {14220067},

year  = {2020},

date = {2020-01-01},

journal = {International Journal of Molecular Sciences},

volume = {21},

number = {2},

publisher = {MDPI AG},

abstract = {β-N-Acetylhexosaminidases are glycoside hydrolases (GHs) acting on N-acetylated carbohydrates and glycoproteins with the release of N-acetylhexosamines. Members of the family GH20 have been reported to catalyze the transfer of N-acetylglucosamine (GlcNAc) to an acceptor, i.e., the reverse of hydrolysis, thus representing an alternative to chemical oligosaccharide synthesis. Two putative GH20 β-N-acetylhexosaminidases, PhNah20A and PhNah20B, encoded by the marine bacterium Paraglaciecola hydrolytica S66T, are distantly related to previously characterized enzymes. Remarkably, PhNah20A was located by phylogenetic analysis outside clusters of other studied β-N-acetylhexosaminidases, in a unique position between bacterial and eukaryotic enzymes. We successfully produced recombinant PhNah20A showing optimum activity at pH 6.0 and 50◦C, hydrolysis of GlcNAc β-1,4 and β-1,3 linkages in chitobiose (GlcNAc)2 and GlcNAc-1,3-β-Gal-1,4-β-Glc (LNT2), a human milk oligosaccharide core structure. The kinetic parameters of PhNah20A for p-nitrophenyl-GlcNAc and p-nitrophenyl-GalNAc were highly similar: kcat /KM being 341 and 344 mM−1 s−1, respectively. PhNah20A was unstable in dilute solution, but retained full activity in the presence of 0.5% bovine serum albumin (BSA). PhNah20A catalyzed the formation of LNT2, the non-reducing trisaccharide β-Gal-1,4-β-Glc-1,1-β-GlcNAc, and in low amounts the β-1,2-or β-1,3-linked trisaccharide β-Gal-1,4(β-GlcNAc)-1,x-Glc by a transglycosylation of lactose using 2-methyl-(1,2-dideoxy-α-d-glucopyrano)-oxazoline (NAG-oxazoline) as the donor. PhNah20A is the first characterized member of a distinct subgroup within GH20 β-N-acetylhexosaminidases.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{10.3389/fnagi.2020.00103,

title = {Resveratrol Derivatives as Potential Treatments for Alzheimer’s and Parkinson’s Disease},

author = {Bruno Dutra Arbo and Corinne André-Miral and Raif Gregorio Nasre-Nasser and Lúcia Emanueli Schimith and Michele Goulart Santos and Dennis Costa-Silva and Ana Luiza Muccillo-Baisch and Mariana Appel Hort},

url = {https://www.frontiersin.org/article/10.3389/fnagi.2020.00103},

doi = {10.3389/fnagi.2020.00103},

issn = {1663-4365},

year  = {2020},

date = {2020-01-01},

urldate = {2020-01-01},

journal = {Frontiers in Aging Neuroscience},

volume = {12},

pages = {103},

abstract = {Neurodegenerative diseases are characterized by the progressive loss of neurons in different regions of the nervous system. Alzheimer’s disease (AD) and Parkinson’s disease (PD) are the two most prevalent neurodegenerative diseases, and the symptoms associated with these pathologies are closely related to the regions that are most affected by the process of neurodegeneration. Despite their high prevalence, currently, there is no cure or disease-modifying drugs for the treatment of these conditions. In the last decades, due to the need for the development of new treatments for neurodegenerative diseases, several authors have investigated the neuroprotective actions of naturally occurring molecules, such as resveratrol. Resveratrol is a stilbene found in several plants, including grapes, blueberries, raspberries, and peanuts. Studies have shown that resveratrol presents neuroprotective actions in experimental models of AD and PD, however, its clinical application is limited due to its rapid metabolism and low bioavailability. In this context, studies have proposed that structural changes in the resveratrol molecule, including glycosylation, alkylation, halogenation, hydroxylation, methylation, and prenylation could lead to the development of derivatives with enhanced bioavailability and pharmacological activity. Therefore, this review article aims to discuss how resveratrol derivatives could represent viable molecules in the search for new drugs for the treatment of AD and PD.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{doi:10.1021/acs.joc.0c01927b,

title = {Access to Galectin-3 Inhibitors from Chemoenzymatic Synthons},

author = {Christophe Dussouy and Stéphane Téletchéa and Annie Lambert and Cathy Charlier and Iuliana Botez and Frédéric De Ceuninck and Cyrille Grandjean},

url = {https://doi.org/10.1021/acs.joc.0c01927},

doi = {10.1021/acs.joc.0c01927},

year  = {2020},

date = {2020-01-01},

journal = {The Journal of Organic Chemistry},

volume = {85},

number = {24},

pages = {16099-16114},

abstract = {Chemoenzymatic strategies are useful for providing both regio- and stereoselective access to bioactive oligosaccharides. We show herein that a glycosynthase mutant of a Thermus thermophilus α-glycosidase can react with unnatural glycosides such as 6-azido-6-deoxy-d-glucose/glucosamine to lead to β-d-galactopyranosyl-(1→3)-d-glucopyranoside or β-d-galactopyranosyl-(1→3)-2-acetamido-2-deoxy-d-glucopyranoside derivatives bearing a unique azide function. Taking advantage of the orthogonality between the azide and the hydroxyl functional groups, the former was next selectively reacted to give rise to a library of galectin-3 inhibitors. Combining enzyme substrate promiscuity and bioorthogonality thus appears as a powerful strategy to rapidly access to sugar-based ligands},

note = {PMID: 33200927},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Bogoeva2019,

title = {Binding of Gold(III) Porphyrin by the Pro-metastatic Regulatory Protein Human Galectin-3},

author = {Vanya Bogoeva and Miroslav Rangelov and Nadezhda Todorova and Annie Lambert and Clarisse Bridot and Anna Yordanova and Goedele Roos and Cyrille Grandjean and Julie Bouckaert},

doi = {10.3390/molecules24244561},

issn = {14203049},

year  = {2019},

date = {2019-12-01},

journal = {Molecules},

volume = {24},

number = {24},

publisher = {MDPI AG},

abstract = {Gold(III) porphyrin presents an attractive alternative to the use of, for example, cisplatin in chemotherapy. However, approaches that allow to selectively target cancer cells are highly sought. Many plant and mammalian lectins have been shown to bind oligosaccharide sequences of the aberrant glycosylation pattern found on cancerous tumors. For example human galectin-3, of the galectin family specific for ß-galactoside, is overexpressed in the extracellular matrix of tumorigenous and metastatic tissues. We searched for non-carbohydrate ligands for galectin-3 that can guide a cytotoxic drug to the cancer cells by maintaining its affinity for tumor associated carbohydrate antigens. Previous findings showed that zinc tetrasulfonatophenylporphyrin can bind galectin-3 with sub-micromolar affinity without disturbing lactose binding. Gold(III) porphyrin is not only cytotoxic to cancer cells, it knows also a potential application as photosensitiser in photodynamic therapy. We investigated the binding of gold(III) porphyrin to galectin-3 using different biophysical interaction techniques and demonstrated a low micromolar affinity of human galectin-3 for the cytotoxic compound. Co-crystallization attempts in order to understand the binding mode of gold porphyrin to galectin-3 failed, but molecular docking emphasized a highly populated secondary binding site that does not hinder lactose or Thomsen Friendenreich disaccharide binding. This suggests that gold(III) porphyrin might significantly enhance its concentration and delivery to cancer cells by binding to human galectin-3 that keeps its orientation towards tumor associated carbohydrate antigens.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Brissonnet2019a,

title = {Monitoring glycosidase activity for clustered sugar substrates, a study on β-glucuronidase},

author = {Yoan Brissonnet and Guillaume Compain and Brigitte Renoux and Eva Maria Krammer and Franck Daligault and David Deniaud and Sébastien Papot and Sébastien G Gouin},

doi = {10.1039/c9ra08847d},

issn = {20462069},

year  = {2019},

date = {2019-01-01},

journal = {RSC Advances},

volume = {9},

number = {69},

pages = {40263--40267},

abstract = {Determination of glycosidase hydrolysis kinetics for a monovalent sugar substrate is relatively straightforward and classically achieved by monitoring the fluorescence signal released from the sugar-conjugated probe after enzymatic hydrolysis. Naturally occuring sugar epitopes are, however, often clustered on biopolymers or at biological surfaces, and previous reports have shown that glycosidase hydrolytic rates can differ greatly with multivalent presentation of the sugar epitopes. New probes are needed to make it easier to interpret the importance of substrate clustering towards a specific enzyme activity. In this work, we developed multivalent glucuronide substrates attached to fluorescent amino-coumarines through self-immolative linkers to enable real time-monitoring of the hydrolysing activity of E.coli β-glucuronidases (GUS) towards clustered substrates. GUS are exoglycosidases of considerable therapeutic interest cleaving β-d-glucuronides and are found in the lysosomes, in the tumoral microenvironment, and are expressed by gut microbiota. GUS showed a much lower catalytic efficiency in hydrolysing clustered glucuronides due to a significantly lower enzymatic velocity and affinity for the substrates. GUS was 52-fold less efficient in hydrolysing GlcA substrates presented on an octameric silsequioxane (COSS) compared with a monovalent GlcA of similar chemical structure. Thus, kinetic and thermodynamic data of GUS hydrolysis towards multivalent glucuronides were easily obtained with these new types of enzymatically-triggered probes. More generally, adapting the substrate nature and valency of these new probes, should improve understanding of the impact of multivalency for a specific enzyme.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Brinkø2019,

title = {Combining Click Reactions for the One-Pot Synthesis of Modular Biomolecule Mimetics},

author = {Anne Brinkø and Christian Risinger and Annie Lambert and Ola Blixt and Cyrille Grandjean and Henrik H Jensen},

doi = {10.1021/acs.orglett.9b02811},

issn = {15237052},

year  = {2019},

date = {2019-01-01},

journal = {Organic Letters},

volume = {21},

number = {18},

pages = {7544--7548},

abstract = {Here, we report on the first combined one-pot use of the two so-called "click reactions": The thiol-ene coupling and the copper-catalyzed alkyne-azide cycloaddition. These reactions were employed in an alternating and one-pot fashion to combine appropriately functionalized monomeric carbohydrate building blocks to create mimics of trisaccharides and tetrasaccharides as single anomers, with only minimal purification necessary. The deprotected oligosaccharide mimics were found to bind both plant lectins and human galectin-3.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Pillot2019,

title = {Site-Specific Conjugation for Fully Controlled Glycoconjugate Vaccine Preparation},

author = {Aline Pillot and Alain Defontaine and Amina Fateh and Annie Lambert and Maruthi Prasanna and Mathieu Fanuel and Muriel Pipelier and Noemi Csaba and Typhaine Violo and Emilie Camberlein and Cyrille Grandjean},

doi = {10.3389/fchem.2019.00726},

issn = {22962646},

year  = {2019},

date = {2019-01-01},

journal = {Frontiers in Chemistry},

volume = {7},

number = {November},

pages = {1--9},

abstract = {Glycoconjugate vaccines are formed by covalently link a carbohydrate antigen to a carrier protein whose role is to achieve a long lasting immune response directed against the carbohydrate antigen. The nature of the sugar antigen, its length, its ratio per carrier protein and the conjugation chemistry impact on both structure and the immune response of a glycoconjugate vaccine. In addition it has long been assumed that the sites at which the carbohydrate antigen is attached can also have an impact. These important issue can now be addressed owing to the development of novel chemoselective ligation reactions as well as techniques such as site-selective mutagenesis, glycoengineering, or extension of the genetic code. The preparation and characterization of homogeneous bivalent pneumococcal vaccines is reported. The preparation and characterization of homogeneous bivalent pneumococcal vaccines is reported. A synthetic tetrasaccharide representative of the serotype 14 capsular polysaccharide of Streptococcus pneumoniae has been linked using the thiol/maleimide coupling chemistry to four different Pneumococcal surface adhesin A (PsaA) mutants, each harboring a single cysteine mutation at a defined position. Humoral response of these 1 to 1 carbohydrate antigen/PsaA conjugates have been assessed in mice. Our results showed that the carbohydrate antigen-PsaA connectivity impacts the anti-carrier response and raise questions about the design of glycoconjugate vaccine whereby the protein plays the dual role of immunogen and carrier.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{PRASANNA201931,

title = {Semisynthetic glycoconjugate based on dual role protein/PsaA as a pneumococcal vaccine},

author = {Maruthi Prasanna and Daphnée Soulard and Emilie Camberlein and Nicolas Ruffier and Annie Lambert and François Trottein and Noemi Csaba and Cyrille Grandjean},

url = {http://www.sciencedirect.com/science/article/pii/S0928098718305487},

doi = {https://doi.org/10.1016/j.ejps.2018.12.013},

issn = {0928-0987},

year  = {2019},

date = {2019-01-01},

journal = {European Journal of Pharmaceutical Sciences},

volume = {129},

pages = {31--41},

abstract = {Pneumococcal infections remain a major public health concern worldwide. The currently available vaccines in the market are based on pneumococcal capsular polysaccharides but they still need to be improved to secure an optimal coverage notably in population at risk. To circumvent this, association of virulence pneumococcal proteins to the polysaccharide valencies has been proposed with the hope to observe an additive - if not synergistic - protective effect. Along this line, the use of the highly conserved and ubiquitous pneumococcal surface adhesin A (PsaA) as a protein carrier for a synthetic pneumococcal oligosaccharide is demonstrated herein for the first time. A tetrasaccharide mimicking functional antigenic determinants from the S. pneumoniae serotype 14 capsular polysaccharide (Pn14TS) was chemically synthesised. The mature PsaA (mPsaA) was expressed in E. coli and purified using affinity chromatography. The Pn14PS was conjugated to mPsaA using maleimide-thiol coupling chemistry to obtain mPsaA-Pn14PS conjugate (protein/sugar molar ratio: 1/5.4). The mPsaA retained the structural conformation after the conjugation and lyophilisation. The prepared glycoconjugate adjuvanted with α-galactosylceramide, a potent activator of invariant Natural Killer T cells, was tested in mice for its immunological response upon subcutaneous injection in comparison with mPsaA alone and a model BSA conjugate (BSA-Pn14PS, used here as a control). Mice immunised with the mPsaA-Pn14TS produced a robust IgG response against mPsaA and against the capsular polysaccharide from pneumococcal serotype 14. These data provide the basis for novel pneumococcal vaccine development.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Brissonnet2019b,

title = {Multivalent Thiosialosides and Their Synergistic Interaction with Pathogenic Sialidases},

author = {Yoan Brissonnet and Coralie Assailly and Amélie Saumonneau and Julie Bouckaert and Mike Maillasson and Clémence Petitot and Benoit Roubinet and Blanka Didak and Ludovic Landemarre and Clarisse Bridot and Ralf Blossey and David Deniaud and Xibo Yan and Julien Bernard and Charles Tellier and Cyrille Grandjean and Franck Daligault and Sébastien G Gouin},

doi = {10.1002/chem.201805790},

issn = {15213765},

year  = {2019},

date = {2019-01-01},

journal = {Chemistry - A European Journal},

volume = {25},

number = {9},

pages = {2358--2365},

abstract = {Sialidases (SAs) hydrolyze sialyl residues from glycoconjugates of the eukaryotic cell surface and are virulence factors expressed by pathogenic bacteria, viruses, and parasites. The catalytic domains of SAs are often flanked with carbohydrate-binding module(s) previously shown to bind sialosides and to enhance enzymatic catalytic efficiency. Herein, non-hydrolyzable multivalent thiosialosides were designed as probes and inhibitors of V. cholerae, T. cruzi, and S. pneumoniae (NanA) sialidases. NanA was truncated from the catalytic and lectinic domains (NanA-L and NanA-C) to probe their respective roles upon interacting with sialylated surfaces and the synthetically designed di- and polymeric thiosialosides. The NanA-L domain was shown to fully drive NanA binding, improving affinity for the thiosialylated surface and compounds by more than two orders of magnitude. Importantly, each thiosialoside grafted onto the polymer was also shown to reduce NanA and NanA-C catalytic activity with efficiency that was 3000-fold higher than that of the monovalent thiosialoside reference. These results extend the concept of multivalency for designing potent bacterial and parasitic sialidase inhibitors.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Naretto2019,

title = {The agar-specific hydrolase ZgAgaC from the marine bacterium Zobellia galactanivorans defines a new GH16 protein subfamily},

author = {Anaïs Naretto and Mathieu Fanuel and David Ropartz and Hélène Rogniaux and Robert Larocque and Mirjam Czjzek and Charles Tellier and Gurvan Michel},

doi = {10.1074/jbc.RA118.006609},

issn = {1083351X},

year  = {2019},

date = {2019-01-01},

journal = {Journal of Biological Chemistry},

volume = {294},

number = {17},

pages = {6923--6939},

abstract = {Agars are sulfated galactans from red macroalgae and are composed of a D-galactose (G unit) and L-galactose (L unit) alternatively linked by α-1, 3 and β-1, 4 glycosidicbonds. The sepolysaccharides display high complexity, with numerous modifications of their backbone (e.g. presence of a 3, 6-anhydro-bridge (LA unit) and sulfations and methylation). Currently, bacterial polysaccharidases that hydrolyze agars (α-agarases and α-porphyranases) have been characterized on simple agarose and more rarely on porphyran, a polymer containing both agarobiose (G-LA) and porphyranobiose (GL6S) motifs. How bacteria can degrade complex agars remains therefore an open question. Here, we studied an enzyme from the marine bacterium Zobellia galactanivorans (ZgAgaC) that is distantly related to the glycoside hydrolase 16 (GH16) family α-agarases and α-porphyranases. Using a large red algae collection, we demonstrate that ZgAgaC hydrolyzes not only agarose but also complex agars from Ceramiales species. Using tandem MS analysis, we elucidated the structure of a purified hexasaccharide product, L6S-G-LA2Me-G(2Pentose)-LA2S-G, released by the activity of ZgAgaC on agar extracted from Osmundea pinnatifida. By resolving the crystal structure of ZgAgaC at high resolution (1.3 Å) and comparison with the structures of ZgAgaB and ZgPorA in complex with their respective substrates, we determined that ZgAgaC recognizes agarose via a mechanism different from that of classical α-agarases. Moreover, we identified conserved residues involved in the binding of complex oligoagars and demonstrate a probable influence of the acidic polysaccharide's pH microenvironment on hydrolase activity. Finally, a phylogenetic analysis supported the notion that ZgAgaC homologs define a new GH16 subfamily distinct from α-porphyranases and classical α-agarases.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{10.1093/protein/gzz032,

title = {Toward the design of efficient transglycosidases: the case of the GH1 of Thermus thermophilus},

author = {Benoit David and Philippe Arnaud and Charles Tellier and Yves-Henri Sanejouand},

url = {https://doi.org/10.1093/protein/gzz032},

doi = {10.1093/protein/gzz032},

issn = {1741-0126},

year  = {2019},

date = {2019-01-01},

journal = {Protein Engineering, Design and Selection},

volume = {32},

number = {7},

pages = {309--316},

abstract = {Using the information available in the sequences of well-characterized transglycosidases found in plants, mutations were introduced in the glycoside hydrolase of the bacterium Thermus thermophilus, with the aim of turning it into an efficient transglycosidase. All mutants happen to have fair catalytic efficiencies, being at worst 25 times less efficient than the wild type. Noteworthy, W120F, one of our high transglycosylation yield (≈ 50%) mutants, is only two times less efficient than the wild type. Interestingly, while in the wild type the sidechain of the acid–base is only found able to sample a pair of equivalent conformations during 0.5-µs-long molecular dynamics simulations, its flexibility is much higher in the case of the high transglycosylation yield mutants. Our results thus suggest that engineering the flexibility of the acid–base of a retaining glycoside hydrolase could be a general way to turn it into an efficient transglycosidase.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Dion2017c,

title = {Lactosamine-Based Derivatives as Tools to Delineate the Biological Functions of Galectins: Application to Skin Tissue Repair},

author = {Johann Dion and Frédérique Deshayes and Nataliya Storozhylova and Tamara Advedissian and Annie Lambert and Mireille Viguier and Charles Tellier and Christophe Dussouy and Françoise Poirier and Cyrille Grandjean},

doi = {10.1002/cbic.201600673},

issn = {14397633},

year  = {2017},

date = {2017-01-01},

journal = {ChemBioChem},

volume = {18},

number = {8},

pages = {782--789},

abstract = {Galectins have been recognized as potential novel therapeutic targets for the numerous fundamental biological processes in which they are involved. Galectins are key players in homeostasis, and as such their expression and function are finely tuned in vivo. Thus, their modes of action are complex and remain largely unexplored, partly because of the lack of dedicated tools. We thus designed galectin inhibitors from a lactosamine core, functionalized at key C2 and C3′ positions by aromatic substituents to ensure both high affinity and selectivity, and equipped with a spacer that can be modified on demand to further modulate their physico-chemical properties. As a proof-of-concept, galectin-3 was selectively targeted. The efficacy of the synthesized di-aromatic lactosamine tools was shown in cellular assays to modulate collective epithelial cell migration and to interfere with actin/cortactin localization.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Coppin2017,

title = {Galectin-3 is a non-classic RNA binding protein that stabilizes the mucin MUC4 mRNA in the cytoplasm of cancer cells},

author = {Lucie Coppin and Audrey Vincent and Frédéric Frénois and Belinda Duch{ê}ne and Fatima Lahdaoui and Laurence Stechly and Florence Renaud and Céline Villenet and Isabelle Van Seuningen and Emmanuelle Leteurtre and Johann Dion and Cyrille Grandjean and Fran{ç}oise Poirier and Martin Figeac and Delphine Delacour and Nicole Porchet and Pascal Pigny},

doi = {10.1038/srep43927},

issn = {20452322},

year  = {2017},

date = {2017-01-01},

journal = {Scientific Reports},

volume = {7},

number = {March},

pages = {1--14},

abstract = {Pancreatic cancer cells express high levels of MUC1, MUC4 and MUC16 mRNAs that encode membrane-bound mucins. These mRNAs share unusual features such as a long half-life. However, it remains unknown how mucin mRNA stability is regulated. Galectin-3 (Gal-3) is an endogenous lectin playing important biological functions in epithelial cells. Gal-3 is encoded by LGALS3 which is up-regulated in pancreatic cancer. Despite the absence of a RNA-recognition motif, Gal-3 interacts indirectly with pre-mRNAs in the nucleus and promotes constitutive splicing. However a broader role of Gal-3 in mRNA fate is unexplored. We report herein that Gal-3 increases MUC4 mRNA stability through an intermediate, hnRNP-L which binds to a conserved CA repeat element in the 3′UTR in a Gal-3 dependent manner and also controls Muc4 mRNA levels in epithelial tissues of Gal3-/- mice. Gal-3 interacts with hnRNP-L in the cytoplasm, especially during cell mitosis, but only partly associates with protein markers of P-Bodies or Stress Granules. By RNA-IP plus RNA-seq analysis and imaging, we demonstrate that Gal-3 binds to mature spliced MUC4 mRNA in the perinuclear region, probably in hnRNP-L-containing RNA granules. Our findings highlight a new role for Gal-3 as a non-classic RNA-binding protein that regulates MUC4 mRNA post-transcriptionally.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Alvarez-Dorta2017,

title = {Magnetic Nanoparticles Coated with Thiomannosides or Iminosugars to Switch and Recycle Galactosidase Activity},

author = {Dimitri Alvarez-Dorta and Yoan Brissonnet and Amélie Saumonneau and David Deniaud and Julien Bernard and Xibo Yan and Charles Tellier and Franck Daligault and Sébastien G Gouin},

doi = {10.1002/slct.201702063},

issn = {23656549},

year  = {2017},

date = {2017-01-01},

journal = {ChemistrySelect},

volume = {2},

number = {29},

pages = {9552--9556},

abstract = {Glycosidase effectors have rarely been reported despite their great potential interest in pharmaceutical sciences and industry. Magnetic nanoparticles were coated with thiomannosides (SMan@Fe3O4) or the broad spectrum glycosidase inhibitor deoxynojirimycin (DNJ@Fe3O4). The coated ligands were shown to exert a fully reverse effect on a model galactosidase (AgaB), with SMan@Fe3O4 or DNJ@Fe3O4 ligands acting as an enzyme inhibitor (Ki=3.7 µM) or a strong activator (250% higher AgaB velocity at 50 µM), respectively. This is striking considering that monovalent soluble SMan and DNJ analogues do not interact with AgaB at millimolar concentrations. The AgaB-DNJ@Fe3O4 enzyme-effector complex could be magnetically recycled and still showed a higher activity compared to free AgaB after four catalytic cycles. The “boost and recycle” procedure may provide interesting perspectives in glycosidase biocatalysis.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Legentil2017,

title = {Regioselective Galactofuranosylation for the Synthesis of Disaccharide Patterns Found in Pathogenic Microorganisms},

author = {Laurent Legentil and Yari Cabezas and Olivier Tasseau and Charles Tellier and Franck Daligault and Vincent Ferri{è}res},

doi = {10.1021/acs.joc.7b00565},

issn = {15206904},

year  = {2017},

date = {2017-01-01},

journal = {Journal of Organic Chemistry},

volume = {82},

number = {14},

pages = {7114--7122},

abstract = {Koenigs-Knorr glycosylation of acceptors with more than one free hydroxyl group by 2,3,5,6-tetrabenzoyl galactofuranosyl bromide was performed using diphenylborinic acid 2-aminoethyl ester (DPBA) as inducer of regioselectivity. High regioselectivity for the glycosylation on the equatorial hydroxyl group of the acceptor was obtained thanks to the transient formation of a borinate adduct of the corresponding 1,2-cis diol. Nevertheless formation of orthoester byproducts hampered the efficiency of the method. Interestingly electron-withdrawing groups on O-6 or on C-1 of the acceptor displaced the reaction in favor of the desired galactofuranosyl containing disaccharide. The best yield was obtained for the furanosylation of p-nitrophenyl 6-O-acetyl mannopyranoside. Precursors of other disaccharides, found in the glycocalix of some pathogens, were synthesized according to the same protocol with yields ranging from 45 to 86%. This is a good alternative for the synthesis of biologically relevant glycoconjugates.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{David2017a,

title = {Internal Water Dynamics Control the Transglycosylation/Hydrolysis Balance in the Agarase (AgaD) of Zobellia galactanivorans},

author = {Benoit David and Romain Irague and Diane Jouanneau and Franck Daligault and Mirjam Czjzek and Yves-Henri Sanejouand and Charles Tellier},

doi = {10.1021/acscatal.7b00348},

issn = {21555435},

year  = {2017},

date = {2017-01-01},

journal = {ACS Catalysis},

volume = {7},

number = {5},

pages = {3357--3367},

abstract = {In retaining glycoside hydrolases (GHs), transglycosylase activity is often low due to the natural hydrolytic activity that is favored in water. Improving the relative transglycosylase activity of these enzymes is of particular interest to obtain enzymes suitable for the synthesis of oligosaccharides. We explored the effect of engineering the water dynamics within the endo-β-agarase AgaD on the transglycosylation/hydrolysis (T/H) balance. By mutating three amino acids (D341, Q342, and S351), which could control water access to a putative water channel ending close to the active site, we obtained AgaD variants with an inverted T/H balance. For the best mutant, D341L/Q342H/S351F, the hydrolysis activity was reduced 50-fold in comparison to the wild type, while the transglycosylase activity was maintained and even slightly improved. This variant produced a large amount of oligo-agaroses by a disproportionation reaction with deca-agarose as the substrate. Molecular dynamics simulations showed that these enzymatic modifications were correlated with higher water dynamics, as revealed by a marked reduction in the water survival time and a decrease in the purge time of water in a channel ending close to the active site. These results suggest that modifying the water dynamics in GHs could be a rational basis for engineering of transglycosylase activity.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Dion2017a,

title = {Development of a Sensitive Microarray Platform for the Ranking of Galectin Inhibitors: Identification of a Selective Galectin-3 Inhibitor},

author = {Johann Dion and Tamara Advedissian and Nataliya Storozhylova and Samir Dahbi and Annie Lambert and Frédérique Deshayes and Mireille Viguier and Charles Tellier and Françoise Poirier and Stéphane Téletchéa and Christophe Dussouy and Hiroaki Tateno and Jun Hirabayashi and Cyrille Grandjean},

doi = {10.1002/cbic.201700544},

issn = {14397633},

year  = {2017},

date = {2017-01-01},

journal = {ChemBioChem},

volume = {18},

number = {24},

pages = {2428--2440},

abstract = {Glycan microarrays are useful tools for lectin glycan profiling. The use of a glycan microarray based on evanescent-field fluorescence detection was herein further extended to the screening of lectin inhibitors in competitive experiments. The efficacy of this approach was tested with 2/3′-mono- and 2,3′-diaromatic type II lactosamine derivatives and galectins as targets and was validated by comparison with fluorescence anisotropy proposed as an orthogonal protein interaction measurement technique. We showed that subtle differences in the architecture of the inhibitor could be sensed that pointed out the preference of galectin-3 for 2′-arylamido derivatives over ureas, thioureas, and amines and that of galectin-7 for derivatives bearing an α substituent at the anomeric position of glucosamine. We eventually identified a diaromatic oxazoline as a highly specific inhibitor of galectin-3 versus galectin-1 and galectin-7.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Forato2016,

title = {Comparison of Zirconium Phosphonate-Modified Surfaces for Immobilizing Phosphopeptides and Phosphate-Tagged Proteins},

author = {Florian Forato and Hao Liu and Roland Benoit and Franck Fayon and Cathy Charlier and Amina Fateh and Alain Defontaine and Charles Tellier and Daniel R Talham and Clémence Queffélec and Bruno Bujoli},

doi = {10.1021/acs.langmuir.6b01020},

issn = {15205827},

year  = {2016},

date = {2016-01-01},

journal = {Langmuir},

volume = {32},

number = {22},

pages = {5480--5490},

abstract = {Different routes for preparing zirconium phosphonate-modified surfaces for immobilizing biomolecular probes are compared. Two chemical-modification approaches were explored to form self-assembled monolayers on commercially available primary amine-functionalized slides, and the resulting surfaces were compared to well-characterized zirconium phosphonate monolayer-modified supports prepared using Langmuir-Blodgett methods. When using POCl3 as the amine phosphorylating agent followed by treatment with zirconyl chloride, the result was not a zirconium-phosphonate monolayer, as commonly assumed in the literature, but rather the process gives adsorbed zirconium oxide/hydroxide species and to a lower extent adsorbed zirconium phosphate and/or phosphonate. Reactions giving rise to these products were modeled in homogeneous-phase studies. Nevertheless, each of the three modified surfaces effectively immobilized phosphopeptides and phosphopeptide tags fused to an affinity protein. Unexpectedly, the zirconium oxide/hydroxide modified surface, formed by treating the amine-coated slides with POCl3/Zr4+, afforded better immobilization of the peptides and proteins and efficient capture of their targets.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Goux2016,

title = {In vivo phosphorylation of a peptide tag for protein purification},

author = {Marine Goux and Amina Fateh and Alain Defontaine and Mathieu Cinier and Charles Tellier},

url = {https://doi.org/10.1007/s10529-016-2040-4},

doi = {10.1007/s10529-016-2040-4},

issn = {1573-6776},

year  = {2016},

date = {2016-01-01},

journal = {Biotechnology Letters},

volume = {38},

number = {5},

pages = {767--772},

abstract = {To design a new system for the in vivo phosphorylation of proteins in Escherichia coli using the co-expression of the α-subunit of casein kinase II (CKIIα) and a target protein, (Nanofitin) fused with a phosphorylatable tag.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Martin-Jezequel2015,

title = {Effects of organic and inorganic nitrogen on the growth and production of domoic acid by pseudo-nitzschia multiseries and p. Australis (bacillariophyceae) in culture},

author = {Véronique Martin-Jézéquel and Guillaume Calu and Leo Candela and Zouher Amzil and Thierry Jauffrais and Véronique Séchet and Pierre Weigel},

doi = {10.3390/md13127055},

issn = {16603397},

year  = {2015},

date = {2015-12-01},

journal = {Marine Drugs},

volume = {13},

number = {12},

pages = {7067--7086},

publisher = {MDPI AG},

abstract = {Over the last century, human activities have altered the global nitrogen cycle, and anthropogenic inputs of both inorganic and organic nitrogen species have increased around the world, causing significant changes to the functioning of aquatic ecosystems. The increasing frequency of Pseudo-nitzschia spp. in estuarine and coastal waters reinforces the need to understand better the environmental control of its growth and domoic acid (DA) production. Here, we document Pseudo-nitzschia spp. growth and toxicity on a large set of inorganic and organic nitrogen (nitrate, ammonium, urea, glutamate, glutamine, arginine and taurine). Our study focused on two species isolated from European coastal waters: P. multiseries CCL70 and P. australis PNC1. The nitrogen sources induced broad differences between the two species with respect to growth rate, biomass and cellular DA, but no specific variation could be attributed to any of the inorganic or organic nitrogen substrates. Enrichment with ammonium resulted in an enhanced growth rate and cell yield, whereas glutamate did not support the growth of P. multiseries. Arginine, glutamine and taurine enabled good growth of P. australis, but without toxin production. The highest DA content was produced when P. multiseries grew with urea and P. australis grew with glutamate. For both species, growth rate was not correlated with DA content but more toxin was produced when the nitrogen source could not sustain a high biomass. A significant negative correlation was found between cell biomass and DA content in P. australis. This study shows that Pseudo-nitzschia can readily utilize organic nitrogen in the form of amino acids, and confirms that both inorganic and organic nitrogen affect growth and DA production. Our results contribute to our understanding of the ecophysiology of Pseudo-nitzschia spp. and may help to predict toxic events in the natural environment.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Segaliny2015,

title = {IL-34 and M-CSF form a novel heteromeric cytokine and regulate the M-CSF receptor activation and localization},

author = {Aude I Ségaliny and Régis Brion and Bénédicte Brulin and Mike Maillasson and Céline Charrier and Stéphane Téletchéa and Dominique Heymann},

doi = {10.1016/j.cyto.2015.05.029},

issn = {10960023},

year  = {2015},

date = {2015-01-01},

journal = {Cytokine},

volume = {76},

number = {2},

pages = {170--181},

abstract = {Interleukin-34 (IL-34) is a newly-discovered homodimeric cytokine that regulates, like Macrophage Colony-Stimulating Factor (M-CSF), the differentiation of the myeloid lineage through M-CSF receptor (M-CSFR) signaling pathways. To date, both cytokines have been considered as competitive cytokines with regard to the M-CSFR. The aim of the present work was to study the functional relationships of these cytokines on cells expressing the M-CSFR. We demonstrate that simultaneous addition of M-CSF and IL-34 led to a specific activation pattern on the M-CSFR, with higher phosphorylation of the tyrosine residues at low concentrations. Similarly, both cytokines showed an additive effect on cellular proliferation or viability. In addition, BIAcore experiments demonstrated that M-CSF binds to IL-34, and molecular docking studies predicted the formation of a heteromeric M-CSF/IL-34 cytokine. A proximity ligation assay confirmed this interaction between the cytokines. Finally, co-expression of the M-CSFR and its ligands differentially regulated M-CSFR trafficking into the cell. This study establishes a new foundation for the understanding of the functional relationship between IL-34 and M-CSF, and gives a new vision for the development of therapeutic approaches targeting the IL-34/M-CSF/M-CSFR axis.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Arab-Jaziri2015,

title = {Enhancing the chemoenzymatic synthesis of arabinosylated xylo-oligosaccharides by GH51 α-l-arabinofuranosidase},

author = {Faten Arab-Jaziri and Bastien Bissaro and Charles Tellier and Michel Dion and Régis Fauré and Michael J O'Donohue},

doi = {10.1016/j.carres.2014.10.029},

issn = {1873426X},

year  = {2015},

date = {2015-01-01},

journal = {Carbohydrate Research},

volume = {401},

pages = {64--72},

publisher = {Elsevier Ltd},

abstract = {Random mutagenesis was performed on the α-l-arabinofuranosidase of Thermobacillus xylanilyticus in order to enhance its ability to perform transarabinofuranosylation using natural xylo-oligosaccharides as acceptors. To achieve this goal, a two-step, high-throughput digital imaging protocol involving a colorimetric substrate was used to screen a library of 30,000 mutants. In the first step this screen selected for hydrolytically-impaired mutants, and in the second step the screen identified mutants whose global activity was improved in the presence of a xylo-oligosaccharide mixture. Thereby, 199 mutants displaying lowered hydrolytic activity and modified properties were detected. In the presence of these xylo-oligosaccharides, most of the 199 (i.e., 70%) enzymes were less inhibited and some (18) mutants displayed an unambiguous alleviation of inhibition (textless25% loss of activity). More precise monitoring of reactions catalyzed by the most promising mutants revealed a significant improvement of the synthesis yields of transglycosylation products (up to 18% compared to 9% for the parental enzyme) when xylobiose was present in the reaction. Genetic analysis of improved mutants revealed that many of the amino acid substitutions that correlate with the modified phenotype are located in the vicinity of the active site, particularly in subsite -1. Consequently, we hypothesize that these mutations modify the active site topology or the molecular interaction network of the l-arabinofuranoside donor substrate, thus impairing the hydrolysis and concomitantly favoring transglycosylation onto natural acceptors.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Andre-Miral2015,

title = {De novo design of a trans-β-N-acetylglucosaminidase activity from a GH1 β-glycosidase by mechanism engineering},

author = {Corinne André-Miral and Fankroma Mt Koné and Claude Solleux and Cyrille Grandjean and Michel Dion and Vinh Tran and Charles Tellier},

doi = {10.1093/glycob/cwu121},

issn = {14602423},

year  = {2015},

date = {2015-01-01},

journal = {Glycobiology},

volume = {25},

number = {4},

pages = {394--402},

abstract = {Glycoside hydrolases are particularly abundant in all areas of metabolism as they are involved in the degradation of natural polysaccharides and glycoconjugates. These enzymes are classified into 133 families (CAZy server, http://www.cazy.org) in which members of each family have a similar structure and catalytic mechanism. In order to understand better the structure/function relationships of these enzymes and their evolution and to develop new robust evolved glycosidases, we undertook to convert a Family 1 thermostable β-glycosidase into an exo-β-N-acetylglucosaminidase. This latter activity is totally absent in Family 1, while natural β-hexosaminidases belong to CAZy Families 3, 20 and 84. Using molecular modeling, we first showed that the docking of N-acetyl-d-glucosamine in the subsite -1 of the β-glycosidase from Thermus thermophilus (TtβGly) suggested several steric conflicts with active site amino-acids (N163, E338) induced by the N-acetyl group. Both N163A and N163D-E338G mutations induced significant N-acetylglucosaminidase activity in TtβGly. The double mutant N163D-E338G was also active on the bicyclic oxazoline substrate, suggesting that this mutated enzyme uses a catalytic mechanism involving a substrate-assisted catalysis with a noncovalent oxazoline intermediate, similar to the N-acetylglucosaminidases from Families 20 and 84. Furthermore, a very efficient trans-N-acetylglucosaminidase activity was observed when the double mutant was incubated in the presence of NAG-oxazoline as a donor and N-methyl-O-benzyl-N-(β-d-glucopyranosyl)-hydroxylamine as an acceptor. More generally, this work demonstrates that it is possible to exchange the specificities and catalytic mechanisms with minimal changes between phylogenetically distant protein structures.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Brissonnet2015,

title = {Polymeric iminosugars improve the activity of carbohydrate-processing enzymes},

author = {Yoan Brissonnet and Simon Ladevèze and David Teze and Emeline Fabre and David Deniaud and Franck Daligault and Charles Tellier and Sergej Šesták and Magali Remaud-Simeon and Gabrielle Potocki-Veronese and Sébastien G Gouin},

doi = {10.1021/acs.bioconjchem.5b00081},

issn = {15204812},

year  = {2015},

date = {2015-01-01},

journal = {Bioconjugate Chemistry},

volume = {26},

number = {4},

pages = {766--772},

abstract = {Multivalent iminosugars have recently emerged as powerful tools to inhibit the activities of specific glycosidases. In this work, biocompatible dextrans were coated with iminosugars to form linear and ramified polymers with unprecedently high valencies (from 20 to 900) to probe the evolution of the multivalent inhibition as a function of ligand valency. This study led to the discovery that polyvalent iminosugars can also significantly enhance, not only inhibit, the enzymatic activity of specific glycoside-hydrolase, as observed on two galactosidases, a fucosidase, and a bacterial mannoside phosphorylase for which an impressive 70-fold activation was even reached. The concept of glycosidase activation is largely unexplored, with a unique recent example of small-molecules activators of a bacterial O-GlcNAc hydrolase. The possibility of using these polymers as "artificial enzyme effectors may therefore open up new perspectives in therapeutics and biocatalysis.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Advedissian2015,

title = {Les galectines: Des lectines pas comme les autres},

author = {Tamara Advedissian and Frédérique Deshayes and Françoise Poirier and Cyrille Grandjean and Mireille Viguier},

doi = {10.1051/medsci/20153105011},

issn = {19585381},

year  = {2015},

date = {2015-01-01},

journal = {Medecine/Sciences},

volume = {31},

number = {5},

pages = {499--505},

abstract = {Galectins constitute a family of soluble animal lectins defined by their evolutionary conserved carbohydrate recognition domain and their affinity for β-galactosides containing glycoconjugates. Each galectin is characterized by a specific spatio-temporal distribution and a unique set of ligands and molecular partners. Interestingly, galectins are found both extracellularly and intracellularly and modulate various cellular processes. Knock-out mutant mice for galectins-1, 3 or 7 are viable but display a wide range of defects under various stress conditions. Indeed, galectins are multifunctional proteins involved in cell-cell and cell-extracellular matrix interactions, organization of membrane domains, cell signalling and also in intracellular trafficking, apoptosis, regulation of cell cycle. Galectins represent potential therapeutic targets, especially in the context of cancer and inflammatory diseases.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Cabezas2015,

title = {Leishmania cell wall as a potent target for antiparasitic drugs. A focus on the glycoconjugates},

author = {Yari Cabezas and Laurent Legentil and Florence Robert-Gangneux and Franck Daligault and Sorya Belaz and Caroline Nugier-Chauvin and Sylvain Tranchimand and Charles Tellier and Jean Pierre Gangneux and Vincent Ferri{è}res},

doi = {10.1039/c5ob00563a},

issn = {14770520},

year  = {2015},

date = {2015-01-01},

journal = {Organic and Biomolecular Chemistry},

volume = {13},

number = {31},

pages = {8393--8404},

publisher = {Royal Society of Chemistry},

abstract = {Although leishmaniasis has been studied for over a century, the fight against cutaneous, mucocutaneous and visceral forms of the disease remains a hot topic. This review refers to the parasitic cell wall and more particularly to the constitutive glycoconjugates. The structures of the main glycolipids and glycoproteins, which are species-dependent, are described. The focus is on the disturbance of the lipid membrane by existing drugs and possible new ones, in order to develop future therapeutic agents.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Teze2015,

title = {Semi-rational approach for converting a GH36 α-glycosidase into an α-transglycosidase},

author = {David Teze and Franck Daligault and Vincent Ferrières and Yves-Henri Sanejouand and Charles Tellier},

doi = {10.1093/glycob/cwu124},

issn = {14602423},

year  = {2015},

date = {2015-01-01},

journal = {Glycobiology},

volume = {25},

number = {4},

pages = {420--427},

abstract = {A large number of retaining glycosidases catalyze both hydrolysis and transglycosylation reactions. In order to use them as catalysts for oligosaccharide synthesis, the balance between these two competing reactions has to be shifted toward transglycosylation. We previously designed a semi-rational approach to convert the Thermus thermophilus β-glycosidases into transglycosidases by mutating highly conserved residues located around the -1 subsite. In an attempt to verify that this strategy could be a generic approach to turn glycosidases into transglycosidases, Geobacillus stearothermophilus α-galactosidase (AgaB) was selected in order to obtain α-transgalactosidases. This is of particular interest as, to date, there are no efficient α-galactosynthases, despite the considerable importance of α-galactooligosaccharides. Thus, by site-directed mutagenesis on 14 AgaB residues, 26 single mutants and 22 double mutants were created and screened, of which 11 single mutants and 6 double mutants exhibited improved synthetic activity, producing 4-nitrophenyl α-d-galactopyranosyl-(1,6)-α-d-galactopyranoside in 26-57% yields against only 22% when native AgaB was used. It is interesting to note that the best variant was obtained by mutating a second-shell residue, with no direct interaction with the substrate or a catalytic amino acid. As this approach has proved to be efficient with both α- and β-glycosidases, it is a promising route to convert retaining glycosidases into transglycosidases.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Saumonneau2015a,

title = {Design of an α-l-transfucosidase for the synthesis of fucosylated HMOs},

author = {Amélie Saumonneau and Elise Champion and Pauline Peltier-Pain and Dora Molnar-Gabor and Johann Hendrickx and Vinh Tran and Markus Hederos and Gyula Dekany and Charles Tellier},

doi = {10.1093/glycob/cwv099},

issn = {14602423},

year  = {2015},

date = {2015-01-01},

journal = {Glycobiology},

volume = {26},

number = {3},

pages = {261--269},

abstract = {Human milk oligosaccharides (HMOs) are recognized as benefiting breast-fed infants in multiple ways. As a result, there is growing interest in the synthesis of HMOs mimicking their natural diversity. Most HMOs are fucosylated oligosaccharides. α-l-Fucosidases catalyze the hydrolysis of α-l-fucose from the non-reducing end of a glucan. They fall into the glycoside hydrolase GH29 and GH95 families. The GH29 family fucosidases display a classic retaining mechanism and are good candidates for transfucosidase activity. We recently demonstrated that the α-l-fucosidase from Thermotoga maritima (TmαFuc) from the GH29 family can be evolved into an efficient transfucosidase by directed evolution (Osanjo et al. 2007). In this work, we developed semi-rational approaches to design an α-l-transfucosidase starting with the α-l-fucosidase from commensal bacteria Bifidobacterium longum subsp. infantis (BiAfcB, Blon-2336). Efficient fucosylation was obtained with enzyme mutants (L321P-BiAfcB and F34I/L321P-BiAfcB) enabling in vitro synthesis of lactodifucotetraose, lacto-N-fucopentaose II, lacto-N-fucopentaose III and lacto-N-difucohexaose I. The enzymes also generated more complex HMOs like fucosylated para-lacto-N-neohexaose (F-p-LNnH) and mono- or difucosylated lacto-N-neohexaose (F-LNnH-I, F-LNnH-II and DF-LNnH). It is worth noting that mutation at these two positions did not result in a strong decrease in the overall activity of the enzyme, which makes these variants interesting candidates for large-scale transfucosylation reactions. For the first time, this work provides an efficient enzymatic method to synthesize the majority of fucosylated HMOs.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}