A Survey of the Role of Noncovalent Sulfur Interactions in Drug Design
A Survey of the Role of Noncovalent Sulfur Interactions in Drug Design
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DOI：
10.1021/jm501853m
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发表时间：
2015-06-11
影响因子：
7.3
通讯作者：
Meanwell, Nicholas A.
中科院分区：
文献类型：
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作者：
Beno, Brett R.;Yeung, Kap-Sun;Meanwell, Nicholas A.
缺电子的二价硫原子具有两个正静电势区域，这是C-S键的低位σ * 轨道的结果，其可用于与包括氧和氮原子以及可能的π系统的电子供体相互作用。分子内相互作用是迄今为止这种效应最常见的表现形式，它提供了一种调节分子构象偏好的方法。虽然是一个有据可查的现象，但药物设计中的先验应用相对较少，并且这种相互作用通常是具有分子内氢键相互作用的电子等排的，似乎未被药物化学界所重视。在这个角度来看，我们讨论了硫σ * 轨道相互作用的理论基础，并说明其在药物设计和有机合成的背景下的重要性。硫相互作用在蛋白质结构和功能的作用进行了讨论，虽然相对罕见，配体C-S σ * 轨道和蛋白质之间的分子间相互作用进行了说明。
Electron deficient, bivalent sulfur atoms have two areas of positive electrostatic potential, a Consequence of the low-lying sigma* orbitals of the C-S bond that are available for interaction with electron donors including oxygen and nitrogen atoms and, possibly, pi-systems. Intramolecular interactions are by far the most common manifestation of this effect, which offers a means of modulating the conformational preferences of a molecule. Although a well-documented phenomenon, a priori applications in drug design are relatively sparse and this interaction, which is often isosteric with an intramolecular hydrogen-bonding interaction, appears to be underappreciated by the medicinal chemistry community. In this Perspective, we discuss the theoretical basis for sulfur sigma* orbital interactions and illustrate their importance in the context of drug design and organic synthesis. The role of sulfur interactions in protein structure and function is discussed and although relatively rare, intermolecular interactions between ligand C-S sigma* orbitals and proteins are illustrated.