@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{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{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{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{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{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}

}