title: Design of a peptidic inhibitor that targets the dimer interface of a prototypic galectin.
abstract: Galectins are small soluble lectins that bind α-galactosides via their carbohydrate recognition domain (CRD). Their ability to dimerize is critical for the crosslinking of glycoprotein receptors and subsequent cellular signaling. This is particularly important in their immunomodulatory role via the induction of T-cell apoptosis. Because galectins play a central role in many pathologies, including cancer, they represent valuable therapeutic targets. At present, most inhibitors have been directed towards the CRD, a challenging task in terms of specificity given the high structural homology of the CRD among galectins. Such inhibitors are not effective at targeting CRD-independent functions of galectins. Here, we report a new class of galectin inhibitors that specifically binds human galectin-7 (hGal-7), disrupts the formation of homodimers, and inhibits the pro-apoptotic activity of hGal-7 on Jurkat T cells. In addition to representing a new means to achieve specificity when targeting galectins, such inhibitors provide a promising alternative to more conventional galectin inhibitors that target the CRD with soluble glycans or other small molecular weight allosteric inhibitors.
authors.affiliation: INRS-Institut Armand-Frappier, Université du Québec, Laval, Québec, H7V 1B7 Canada.
authors.forename: Maria Claudia
authors.initials: MC
authors.lastname: Vladoiu
authors.affiliation: INRS-Institut Armand-Frappier, Université du Québec, Laval, Québec, H7V 1B7 Canada.
authors.forename: Marilyne
authors.initials: M
authors.lastname: Labrie
authors.affiliation: INRS-Institut Armand-Frappier, Université du Québec, Laval, Québec, H7V 1B7 Canada.
authors.forename: Myriam
authors.initials: M
authors.lastname: Létourneau
authors.affiliation: INRS-Institut Armand-Frappier, Université du Québec, Laval, Québec, H7V 1B7 Canada.
authors.forename: Philippe
authors.initials: P
authors.lastname: Egesborg
authors.affiliation: INRS-Institut Armand-Frappier, Université du Québec, Laval, Québec, H7V 1B7 Canada.
authors.forename: Donald
authors.initials: D
authors.lastname: Gagné
authors.affiliation: INRS-Institut Armand-Frappier, Université du Québec, Laval, Québec, H7V 1B7 Canada.
authors.forename: Étienne
authors.initials: É
authors.lastname: Billard
authors.affiliation: INRS-Institut Armand-Frappier, Université du Québec, Laval, Québec, H7V 1B7 Canada.
authors.forename: Andrée-Anne
authors.initials: AA
authors.lastname: Grosset
authors.affiliation: INRS-Institut Armand-Frappier, Université du Québec, Laval, Québec, H7V 1B7 Canada.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Doucet
authors.affiliation: INRS-Institut Armand-Frappier, Université du Québec, Laval, Québec, H7V 1B7 Canada.
authors.forename: David
authors.initials: D
authors.lastname: Chatenet
authors.affiliation: INRS-Institut Armand-Frappier, Université du Québec, Laval, Québec, H7V 1B7 Canada.
authors.forename: Yves
authors.initials: Y
authors.lastname: St-Pierre
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D015195:Drug Design; D037161:Galectins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000235:genetics; D006801:Humans; D019169:Jurkat Cells; D008958:Models, Molecular; D010455:Peptides / Q000138:chemical synthesis / Q000494:pharmacology*; D011485:Protein Binding; D055503:Protein Multimerization / Q000187:drug effects*; D020836:Protein Structure, Quaternary; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology
chemical_list: D037161:Galectins; C092525:LGALS7 protein, human; D010455:Peptides; D011994:Recombinant Proteins
keywords: T-cells; apoptosis; galectin; inhibitor; peptide