Enthalpic (electrostatic) contribution to the chelate effect

A correlation between ligand binding constant and a specific hydrogen bond strength in complexes of glycopeptide antibiotics with cell wall analogues

Mark S. Searle, Gary J. Sharman, Patrick Groves, Bellinda Benhamu, Daniel A. Beauregard, Martin S. Westwell, Robert J. Dancer, Alison J. Maguire, Andrew C. Try, Dudley H. Williams*

*Corresponding author for this work

Research output: Contribution to journalArticle

46 Citations (Scopus)

Abstract

The 1H NMR chemical shift of amide protons in the binding pocket of glycopeptide antibiotics has been used to monitor the interaction of these amide protons with the carboxylate group of cell wall analogues and related ligands. A good correlation is observed between overall ligand binding energy (Δ(Go) and amide NH chemical shift. We conclude that the strength of the electrostatic interaction of the carboxylate group, which is crucial to recognition and binding by the antibiotics, is cooperatively enhanced by adjacent functional groups on the same ligand template. Hydrogen bonding and burial of hydrocarbon in adjacent sites produce an enhancement of electrostatic binding of the carboxylate group. The data provide experimental evidence for an enthalpic contribution to the chelate effect that is distinct from, and works in addition to, the classic entropic chelate effect. The correlation between amide NH chemical shift and overall binding energy has been used to show binding affinity for eremomycin and chloroeremomycin by di-N-Ac-Lys-D-Ala-D-Lac (Lac = lactate), which is a cell wall analogue of bacteria which exhibit vancomycin resistance. Binding constants for this ligand have also been determined by UV difference spectrophotometry (70 dm3 mol-1 and 240 dm3 mol-1 respectively).

Original languageEnglish
Pages (from-to)2781-2786
Number of pages6
JournalJournal of the Chemical Society - Perkin Transactions 1
Issue number23
Publication statusPublished - 7 Dec 1996

Fingerprint Dive into the research topics of 'Enthalpic (electrostatic) contribution to the chelate effect: A correlation between ligand binding constant and a specific hydrogen bond strength in complexes of glycopeptide antibiotics with cell wall analogues'. Together they form a unique fingerprint.

Cite this