The Role of Halogen Bonding in Inhibitor Recognition and Binding by Protein Kinases

Title: The Role of Halogen Bonding in Inhibitor Recognition and Binding by Protein Kinases

Volume: 7 Issue: 14

Author(s): Voth Regier Andrea and Ho Shing P.

Affiliation:

Keywords: Halogen bond, protein kinase, rational drug design

Abstract: Halogen bonds are short-range molecular interactions that are analogous to classical hydrogen bonds, except that a polarized halogen replaces the hydrogen as the acid in the Lewis acid/base pair. Such interactions occur regularly in the structures of many ligand-protein complexes, but have only recently been recognized in biological systems as a distinct class with well-defined physical characteristics. In this review, we survey twelve single crystal structures of protein kinase complexes with halogenated ligands in order to characterize the role of halogen bonds in conferring specificity and affinity for halogenated inhibitors in this important class of enzymes. From this survey, we attempt to identify the properties of halogen bonds that can be generally applied to bottom-up strategies for designing inhibitors for this and other enzyme targets.

Cite this article as:

Andrea Regier Voth and P. Shing Ho, The Role of Halogen Bonding in Inhibitor Recognition and Binding by Protein Kinases, Current Topics in Medicinal Chemistry 2007; 7 (14) . https://dx.doi.org/10.2174/156802607781696846