Principles and Applications of Halogen Bonding in Medicinal Chemistry and Chemical Biology
Principles and Applications of Halogen Bonding in Medicinal Chemistry and Chemical Biology
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DOI：
10.1021/jm3012068
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发表时间：
2013-02-28
影响因子：
7.3
通讯作者：
Boeckler, Frank M.
中科院分区：
文献类型：
--
作者：
Wilcken, Rainer;Zimmermann, Markus O.;Boeckler, Frank M.
卤素键合。在材料科学中已经知道了几十年，但直到最近，蛋白质-配体相互作用中的卤素键在很大程度上是偶然发现的结果，而不是合理的设计。在这个视角下，我们提供了对卤素键合现象的见解，特别是它在药物发现中的作用。我们总结了定义它的强度和方向性的理论背景，对它在蛋白质-配体络合物中的存在和相互作用几何结构进行了系统的分析，并给出了最近成功地利用卤素键来识别和优化铅的例子。根据这些数据，我们讨论了利用卤键进行分子识别和合理药物设计的潜力和局限性。
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.