文献类型：期刊文献

英文题名：Halogen bonding for rational drug design and new drug discovery

作者：Lu, Yunxiang[1,2];Liu, Yingtao[3];Xu, Zhijian[3];Li, Haiying[1,2];Liu, Honglai[1,2];Zhu, Weiliang[3]

机构：[1]E China Univ Sci & Technol, Key Lab Adv Mat, Shanghai 200237, Peoples R China;[2]E China Univ Sci & Technol, Dept Chem, Shanghai 200237, Peoples R China;[3]Chinese Acad Sci, Shanghai Inst Mat Med, Drug Discovery & Design Ctr, Shanghai 201203, Peoples R China

年份：2012

卷号：7

期号：5

起止页码：375

外文期刊名：EXPERT OPINION ON DRUG DISCOVERY

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000303329500002)】；

基金：This work was financially supported by the Natural Science Foundation of Shanghai (Grant No. 11ZR1408700), the National Natural Science Foundation of China (Grant No. 21103047), the Fundamental Research Funds for the Central Universities of China, the International Cooperation Project of MOST (Grant No. 2010DFB73280, W.Z.) and the 973 project (Grant No. 2012CB910403, W.Z.).

语种：英文

外文关键词：binding affinity; drug design; halogen bonding; inhibitors

摘要：Introduction: A large number of drugs and drug candidates in clinical development contain halogen substituents. For a long time, only the steric and lipophilic contributions of halogens were considered when trying to exploit their effects on ligand binding. However, the ability of halogens to form stabilizing interactions, such as halogen bonding, hydrogen bonding and multipolar interactions, in biomolecular systems was revealed recently. Halogen bonding, the non-covalent interaction in which covalently bound halogens interact with Lewis bases, has now been utilized in the context of rational drug design. Areas covered: The purpose of this review is to show how halogen bonding could be used in drug design, and in particular, to stimulate researchers to apply halogen bonding in lead optimization. This review article covers the recent advances relevant to halogen bonding in drug discovery and biological design over the past decade, including database survey of this interaction in protein-ligand complexes, molecular mechanical investigations of halogen bonding in drug discovery and applications of this interaction in the development of halogenated ligands as inhibitors and drugs for protein kinases, serine protease factor Xa, HIV reverse transcriptase and so on. Expert opinion: Halogen bonding should intentionally be used as a powerful tool, comparable with hydrogen bonding, to enhance the binding affinity and also influence the binding selectivity. Rational design of new and potent inhibitors against therapeutic targets through halogen bonding continues to be an exciting area, which will be further elucidated with the combination of various experimental techniques and theoretical calculations in the forthcoming years.