Principles and Applications of Halogen Bonding in Medicinal Chemistry and Chemical Biology

被引：1077

作者：

Wilcken, Rainer ^{[1
,2
]}

Zimmermann, Markus O. ^{[1
]}

Lange, Andreas ^{[1
]}

Joerger, Andreas C. ^{[2
]}

Boeckler, Frank M. ^{[1
]}

机构：

[1] Univ Tubingen, Lab Mol Design & Pharmaceut Biophys, Dept Pharmaceut & Med Chem, Inst Pharm, D-72076 Tubingen, Germany

[2] MRC Lab Mol Biol, Cambridge CB2 0QH, England

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2013年 / 56卷 / 04期

关键词：

RESOLUTION CRYSTAL-STRUCTURES; EMPIRICAL SCORING FUNCTIONS; DENSITY-FUNCTIONAL THEORY; PROTEIN-LIGAND-BINDING; STRUCTURAL BASIS; INTERMOLECULAR INTERACTIONS; FORCE-FIELD; NONNUCLEOSIDE INHIBITORS; GENETIC ALGORITHM; HIGHLY POTENT;

D O I：

10.1021/jm3012068

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Halogen bonding. has been known in material science for decades, but until recently, halogen bonds in protein-ligand interactions were largely the result of serendipitous discovery rather than rational design. In this Perspective, we provide insights into the phenomenon of halogen bonding, with special focus on its role in drug discovery. We summarize the theoretical background defining its strength and directionality, provide a systematic analysis of its occurrence and interaction geometries in protein-ligand complexes, and give recent examples where halogen bonding has been successfully harnessed for lead identification and optimization. In light of these data, we discuss the potential and limitations of exploiting halogen bonds for molecular recognition and rational drug design.

引用

页码：1363 / 1388

页数：26

共 163 条

[1] Mechanism of AMPA Receptor Activation by Partial Agonists DISULFIDE TRAPPING OF CLOSED LOBE CONFORMATIONS [J].