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Toward the Rational Design of Galactosylated Glycoclusters That Target Pseudomonas aeruginosa Lectin A (LecA): Influence of Linker Arms That Lead to Low‐Nanomolar Multivalent Ligands
Author(s) -
Wang Shuai,
Dupin Lucie,
Noël Mathieu,
Carroux Cindy J.,
Renaud Louis,
Géhin Thomas,
Meyer Albert,
Souteyrand Eliane,
Vasseur JeanJacques,
Vergoten Gérard,
Chevolot Yann,
Morvan François,
Vidal Sébastien
Publication year - 2016
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201602047
Subject(s) - linker , lectin , pseudomonas aeruginosa , chemistry , tetramer , biofilm , ligand (biochemistry) , glycoprotein , glycoconjugate , virulence , virulence factor , galactose , microbiology and biotechnology , biochemistry , combinatorial chemistry , bacteria , biology , enzyme , receptor , computer science , gene , genetics , operating system
Anti‐infectious strategies against pathogen infections can be achieved through antiadhesive strategies by using multivalent ligands of bacterial virulence factors. LecA and LecB are lectins of Pseudomonas aeruginosa implicated in biofilm formation. A series of 27 LecA‐targeting glycoclusters have been synthesized. Nine aromatic galactose aglycons were investigated with three different linker arms that connect the central mannopyranoside core. A low‐nanomolar ( K d =19 n m , microarray) ligand with a tyrosine‐based linker arm could be identified in a structure–activity relationship study. Molecular modeling of the glycoclusters bound to the lectin tetramer was also used to rationalize the binding properties observed.