Design and Synthesis of Galactosylated Bifurcated Ligands with Nanomolar Affinity for Lectin LecA from Pseudomonas aeruginosa. (27th April 2017)

• Record Type: Journal Article
• Authors: Angeli, Anthony; Li, Muchen; Dupin, Lucie; Vergoten, Gérard; Noël, Mathieu; Madaoui, Mimouna; Wang, Shuai; Meyer, Albert; Géhin, Thomas; Vidal, Sébastien; Vasseur, Jean‐Jacques; Chevolot, Yann; Morvan, François
• Is Part Of: Chembiochem. Volume 18:Number 11(2017)
• Page Start: 1036
• Page End: 1047
• Publication Date: 2017-04-27
• Subjects: glycoclusters -- LecA -- microarrays -- multivalency -- oligonucleotides -- Pseudomonas aeruginosa; Biochemistry -- Periodicals; Molecular biology -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1002/cbic.201700154
• Languages: English
• ISSNs: 1439-4227

Abstract

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 ( K d ). This has led to high‐affinity LecA ligands with K d values in the low nanomolar range ( K d =22 nm for the best one). Abstract : A series of 32 glycodendrimers of generations 0 and 1 that target lectin A (LecA) were synthesized, and the influences of the multivalent core and of the aglycon on their affinities towards LecA were evaluated both qualitatively and quantitatively. Bis‐galactosides incorporating phenyl and lysine aglycons were able to bind LecA with low‐nanomolar K d values.