Open AccessFunctionalization of a Rigid Divalent Ligand for LecA, a Bacterial Adhesion Lectin
Author(s) -
Fu Ou,
Pukin Aliaksei V.,
Quarles van Ufford H. C.,
Kemmink Johan,
de Mol Nico J.,
Pieters Roland J.
Publication year - 2015
Publication title -
chemistryopen
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.644
H-Index - 29
ISSN - 2191-1363
DOI - 10.1002/open.201402171
Subject(s) - isothermal titration calorimetry , chemistry , lectin , divalent , combinatorial chemistry , surface modification , ligand (biochemistry) , adhesion , biophysics , stereochemistry , titration , biochemistry , organic chemistry , biology , receptor
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).