The bioisosteric similarity of the tetrazole and carboxylate anions: Clues from the topologies of the electrostatic potential and of the electron density
The bioisosteric similarity of the tetrazole and carboxylate anions: Clues from the topologies of the electrostatic potential and of the electron density
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DOI：
10.1016/j.ejmech.2010.01.025
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发表时间：
2010-05-01
影响因子：
6.7
通讯作者：
Weaver, Donald F.
中科院分区：
文献类型：
--
作者：
Matta, Cherif F.;Arabi, Alya A.;Weaver, Donald F.
需要一种先验方法来证明非经典生物电子等排体之间的物理相似性。在这项研究中，我们探索的电子密度和静电势的基础上进行系统的调查生物电子等排体之间的物理和化学相似性的效用。四唑和羧酸酯生物电子等排对用作说明性实例。结果表明，四唑和羧酸根阴离子引起的静电势（ESP）表现出显着的局部相似性的四个共面的局部极小值的位置一致的孤对的处置。这两个生物电子等排体产生的ESP极小值的相似性与它们在原子数量和类型、核几何排列、总体积、部分电荷和电子布居数方面的差异形成鲜明对比。这些极小的拓扑结构和几何配置被证明是独立的模型中使用的封盖组，因此，这个生物电子等排对的固有属性。一个模型的受体区域负责结合到这些生物电子等排体的基础上提出的静电“锁和钥匙”。(C)2010年Elsevier Masson SAS。All rights reserved.
There is a need for an a priori method with which to demonstrate the physical similarities between non-classical bioisosteres. In this study we explore the utility of the electron density and the electrostatic potential as the basis for a systematic investigation of the physical and chemical similarities between bioisosteres. The tetrazole and carboxylate bioisosteric pair is used as an illustrative example. It is shown that tetrazole and carboxylate anions give rise to electrostatic potentials (ESP) that exhibit a remarkable local similarity in the disposition of four coplanar local minima at positions consistent with lone pairs. The similarity of the disposition of these ESP minima generated by the two bioisosteres is in sharp contrast with their differences in the number and types of atoms, their nuclear geometrical arrangements, their total volumes, their partial charges, and their electron populations. The topology and geometrical disposition of these minima are shown to be independent of the capping group used in the model, and thus an inherent property of this bioisosteric pair. A model of the receptor region responsible for binding to either of these bioisosteres is proposed on the basis of an electrostatic "lock-and-key". (C) 2010 Elsevier Masson SAS. All rights reserved.