Design of a peptidic inhibitor that targets the dimer interface of a prototypic galectin
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Maria Claudia Vladoiu1, Marilyne Labrie1, Myriam Létourneau1, Philippe Egesborg1, Donald Gagné1, Étienne Billard1, Andrée-Anne Grosset1, Nicolas Doucet1, David Chatenet1, Yves St-Pierre1
1INRS-Institut Armand-Frappier, Université du Québec, Laval, Québec, H7V 1B7 Canada
Yves St-Pierre, e-mail: firstname.lastname@example.org
Keywords: galectin, inhibitor, peptide, apoptosis, T-cells
Received: May 13, 2015 Accepted: August 20, 2015 Published: October 01, 2015
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.
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