Abstract
Although the halogen bond has attracted much interest in chemistry and material science communities, its implications for drug design are just now coming to light. The protein – ligand interactions through short halogen— oxygen/nitrogen/sulfur contacts have been observed in crystal structures for a long time, but only in recent years, with the experimental and theoretical progress in weak biological interactions, especially the pioneering works contributed by Ho and co-workers (Auffinger, P.; Hays, F. A.; Westhof, E.; Ho, P. S. Proc. Natl. Acad. Sci. USA 2004, 101, 16789 – 16794), these short contacts involving halogens in biomolecules were rediscovered and re-recognized as halogen bonds to stress their shared similarities with hydrogen bonds in strength and directionality. Crystal structure determinations of protein complexes with halogenated ligands preliminarily unveiled the functionality of halogen bonds in protein – ligand recognition. Database surveys further revealed a considerable number of short halogen – oxygen contacts between proteins and halogenated ligands. Theoretical calculations on model and real systems eventually gave a quantitative pronouncement for the substantial contribution of halogen bonds to ligand binding. All of these works forebode that the halogen bond can be exploited as a new and versatile tool for rational drug design and bio-crystal engineering.
Keywords: Halogen bond, -hole, protein-ligand interaction, rational drug design
Mini-Reviews in Medicinal Chemistry
Title: Rediscovery of Halogen Bonds in Protein-Ligand Complexes
Volume: 10 Issue: 4
Author(s): P. Zhou, F. Tian, J. Zou and Z. Shang
Affiliation:
Keywords: Halogen bond, -hole, protein-ligand interaction, rational drug design
Abstract: Although the halogen bond has attracted much interest in chemistry and material science communities, its implications for drug design are just now coming to light. The protein – ligand interactions through short halogen— oxygen/nitrogen/sulfur contacts have been observed in crystal structures for a long time, but only in recent years, with the experimental and theoretical progress in weak biological interactions, especially the pioneering works contributed by Ho and co-workers (Auffinger, P.; Hays, F. A.; Westhof, E.; Ho, P. S. Proc. Natl. Acad. Sci. USA 2004, 101, 16789 – 16794), these short contacts involving halogens in biomolecules were rediscovered and re-recognized as halogen bonds to stress their shared similarities with hydrogen bonds in strength and directionality. Crystal structure determinations of protein complexes with halogenated ligands preliminarily unveiled the functionality of halogen bonds in protein – ligand recognition. Database surveys further revealed a considerable number of short halogen – oxygen contacts between proteins and halogenated ligands. Theoretical calculations on model and real systems eventually gave a quantitative pronouncement for the substantial contribution of halogen bonds to ligand binding. All of these works forebode that the halogen bond can be exploited as a new and versatile tool for rational drug design and bio-crystal engineering.
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Cite this article as:
Zhou P., Tian F., Zou J. and Shang Z., Rediscovery of Halogen Bonds in Protein-Ligand Complexes, Mini-Reviews in Medicinal Chemistry 2010; 10 (4) . https://dx.doi.org/10.2174/138955710791331016
DOI https://dx.doi.org/10.2174/138955710791331016 |
Print ISSN 1389-5575 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5607 |
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