Functionalization of a Rigid Divalent Ligand for LecA, a Bacterial Adhesion Lectin

ChemistryOpen

Ou Fu¹  Dr. Aliaksei V. Pukin¹  H. C. Quarles van Ufford¹  Dr. Johan Kemmink¹  Dr. Nico J. de Mol¹ 

[1] Department of Medicinal Chemistry and Chemical Biology, Utrecht University, Utrecht, The Netherlands

关键词: bacterial lectins;    carbohydrates;    LecA inhibition;    molecular modeling;    multivalency;    virulence factors;   

DOI  :  10.1002/open.201402171

来源: Wiley

【 摘 要 】

Abstract

The bacterial adhesion lectin LecA is an attractive target for interference with the infectivity of its producer P. aeruginosa. Divalent ligands with two terminal galactoside moieties connected by an alternating glucose-triazole spacer were previously shown to be very potent inhibitors. In this study, we chose to prepare a series of derivatives with various new substituents in the spacer in hopes of further enhancing the LecA inhibitory potency of the molecules. Based on the binding mode, modifications were made to the spacer to enable additional spacer–protein interactions. The introduction of positively charged, negatively charged, and also lipophilic functional groups was successful. The compounds were good LecA ligands, but no improved binding was seen, even though altered thermodynamic parameters were observed by isothermal titration calorimetry (ITC).

【 授权许可】

CC BY-NC   
© 2014 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.

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