title: A new approach to explore the binding space of polysaccharide-based ligands: selectin antagonists.
abstract: The discovery of molecules that interfere with the binding of a ligand to a receptor remains a topic of great interest in medicinal chemistry. Herein, we report that a monosaccharide unit of a polysaccharide ligand can be replaced advantageously by a conformationally locked acyclic molecular entity. A cyclic component of the selectin ligand Sialyl Lewis(x), GlcNAc, is replaced by an acyclic tether, tartaric esters, which link two saccharide units. The conformational bias of this acyclic tether originates from the minimization of intramolecular dipole-dipole interaction and the gauche effect. The evaluation of the binding of these derivatives to P-selectin was measured by surface plasmon resonance spectroscopy. The results obtained in our pilot study suggest that the discovery of tunable tethers could facilitate the exploration of the carbohydrate recognition domain of various receptors.
authors.affiliation: Bio-organic Chemistry and Chemical Biology and Peptide Research, Institut de recherches cliniques de Montréal (IRCM) , Montréal, Québec H2W 1R7, Canada.
authors.forename: Mickael
authors.initials: M
authors.lastname: Calosso
authors.affiliation: Bio-organic Chemistry and Chemical Biology and Peptide Research, Institut de recherches cliniques de Montréal (IRCM) , Montréal, Québec H2W 1R7, Canada.
authors.forename: Daniel
authors.initials: D
authors.lastname: Charpentier
authors.affiliation: Bio-organic Chemistry and Chemical Biology and Peptide Research, Institut de recherches cliniques de Montréal (IRCM) , Montréal, Québec H2W 1R7, Canada.
authors.forename: Marc
authors.initials: M
authors.lastname: Vaillancourt
authors.affiliation: Bio-organic Chemistry and Chemical Biology and Peptide Research, Institut de recherches cliniques de Montréal (IRCM) , Montréal, Québec H2W 1R7, Canada.
authors.forename: Mohammed
authors.initials: M
authors.lastname: Bencheqroun
authors.affiliation: Bio-organic Chemistry and Chemical Biology and Peptide Research, Institut de recherches cliniques de Montréal (IRCM) , Montréal, Québec H2W 1R7, Canada.
authors.forename: Gabrielle
authors.initials: G
authors.lastname: St-Pierre
authors.affiliation: Bio-organic Chemistry and Chemical Biology and Peptide Research, Institut de recherches cliniques de Montréal (IRCM) , Montréal, Québec H2W 1R7, Canada.
authors.forename: Brian C
authors.initials: BC
authors.lastname: Wilkes
authors.affiliation: Bio-organic Chemistry and Chemical Biology and Peptide Research, Institut de recherches cliniques de Montréal (IRCM) , Montréal, Québec H2W 1R7, Canada ; Département de Chimie, Université de Montréal , C.P. 6128, succursale Centre-ville, Montréal, Québec H3C 3J7, Canada ; Department of Chemistry, McGill University , Montréal, Québec H3A 2K6, Canada.
authors.forename: Yvan
authors.initials: Y
authors.lastname: Guindon
keywords: Sialyl Lewisx; carbohydrate recognition domain; polysaccharide-based ligands; selectin antagonists; surface plasmon resonance spectroscopy