The influence of the aromatic aglycon of galactoclusters on the binding of LecA: a case study with O-phenyl, S-phenyl, O-benzyl, S-benzyl, O-biphenyl and O-naphthyl aglycons

• DOI: 10.1039/c4ob01599a
• Publication Date: 2014-09-16T15:06:57Z
• Authors: Francesca Casoni; Lucie Dupin; Gérard Vergoten; Albert Meyer; Caroline Ligeour; Thomas Géhin; Olivier Vidal; Eliane Souteyrand; Jean-Jacques Vasseur; Yann Chevolot; François Morvan
• Keywords: Models, Molecular; Azides; [CHIM.ORGA]Chemical Sciences/Organic chemistry; Biphenyl Compounds; Galactose; Galactosides; DNA; Naphthols; mannose-centered tetragalactoclusters; 01 natural sciences; aromatic aglycons; 0104 chemical sciences; di- and triethyleneglycol; phosphodiester; LecA:; galactoclusters; Adhesins, Bacterial

A library of 24 new mannose-centered tetragalactoclusters with four different linkers (di- and triethyleneglycol with phosphodiester or phosphorothioate linkages) and six different aromatic aglycons (O-phenyl, S-phenyl, O-benzyl, S-benzyl, O-biphenyl and O-naphthyl) was synthesized. Their interactions with LecA were evaluated on a DNA Directed Immobilization (DDI) based glycocluster array allowing the determination of their IC50 against lactose and the evaluation of their dissociation constant (Kd). Finally, the docking simulations confirm the experimental results and demonstrated that the better affinity of O-biphenyl- and O-naphthyl-galactoside is due to a double interaction between the aromatic ring and the histidine 50 and proline 51 of LecA.