|
|||||
|
|
Design and Synthesis of Galactosylated Bifurcated Ligands with Nanomolar Affinity for Lectin LecA from Pseudomonas aeruginosa |
|
| Authors: | Dr Anthony Angeli Muchen Li Dr Lucie Dupin Dr Gérard Vergoten Mathieu Noël Mimouna Madaoui Dr Shuai Wang Albert Meyer Thomas Géhin Dr Sébastien Vidal Dr Jean‐Jacques Vasseur Dr Yann Chevolot Dr François Morvan |
| Affiliation: | 1. Institut des Biomolécules Max Mousseron (IBMM), UMR 5247, CNRS, Université Montpellier, ENSCM, Montpellier cedex 5, France;2. Université de Lyon, Institut des Nanotechnologies de Lyon, INL), UMR CNRS 5270, Site Ecole Centrale de Lyon, Ecully cedex, France;3. Unité de Glycobiologie Structurelle et Fonctionnelle, UGSF), UMR 8576 CNRS, Université de Lille 1, Cité Scientifique, Villeneuve d'Ascq cedex, France;4. Institut de Chimie et Biochimie Moléculaires et Supramoléculaires, Laboratoire de Chimie Organique 2, Glycochimie UMR 5246, CNRS, Université Claude Bernard Lyon 1, Villeurbanne, France |
| Abstract: | Lectin A (LecA) from Pseudomonas aeruginosa is an established virulence factor. Glycoclusters that target LecA and are able to compete with human glycoconjugates present on epithelial cells are promising candidates to treat P. aeruginosa infection. A family of 32 glycodendrimers of generation 0 and 1 based on a bifurcated bis‐galactoside motif have been designed to interact with LecA. The influences both of the central multivalent core and of the aglycon of these glycodendrimers on their affinity toward LecA have been evaluated by use of a microarray technique, both qualitatively for rapid screening of the binding properties and also quantitatively (Kd). This has led to high‐affinity LecA ligands with Kd values in the low nanomolar range (Kd=22 nm for the best one). |
| Keywords: | glycoclusters LecA microarrays multivalency oligonucleotides Pseudomonas aeruginosa |