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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 |
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| Authors: | Dr. Shuai Wang Lucie Dupin Mathieu Noël Cindy J. Carroux Dr. Louis Renaud Dr. Thomas Géhin Albert Meyer Dr. Eliane Souteyrand Dr. Jean‐Jacques Vasseur Dr. Gérard Vergoten Dr. Yann Chevolot Dr. François Morvan Dr. Sébastien Vidal |
| Affiliation: | 1. Institut de Chimie et Biochimie Moléculaires et Supramoléculaires, Laboratoire de Chimie Organique 2 - Glycochimie UMR 5246, CNRS - Université Claude Bernard Lyon 1, Villeurbanne, France;2. Institut des Nanotechnologies de Lyon (INL) - UMR CNRS 5270, Ecole Centrale de Lyon, Université de Lyon, Ecully cedex, France;3. Institut des Biomolécules Max Mousseron (IBMM) - UMR 5247, CNRS - Université Montpellier - ENSCM, Montpellier cedex 5, France;4. Institut des Nanotechnologies de Lyon, UMR CNRS 5270, Université Claude Bernard Lyon 1, Université de Lyon, Villeurbanne, France;5. Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576, CNRS - Université de Lille 1, Cité Scientifique, Villeneuve d'Ascq cedex, France |
| Abstract: | 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 (Kd=19 nm , 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. |
| Keywords: | glycoclusters microarrays multivalency oligonucleotides Pseudomonas aeruginosa |