Pharmacophore-guided lead optimization: The rational design of a non-zinc coordinating, sub-micromolar inhibitor of the botulinum neurotoxin serotype a metalloprotease
Pharmacophore-guided lead optimization: The rational design of a non-zinc coordinating, sub-micromolar inhibitor of the botulinum neurotoxin serotype a metalloprotease
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DOI：
10.1016/j.bmcl.2009.01.111
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发表时间：
2009-10-01
影响因子：
2.7
通讯作者：
Bavari, S.
中科院分区：
文献类型：
--
作者：
Burnett, J. C.;Wang, C.;Bavari, S.
肉毒杆菌神经毒素，负责神经麻痹综合症肉毒中毒，是最致命的已知生物毒素。本研究中描述的工作是基于肉毒杆菌神经毒素血清型a轻链抑制的三区药效团模型。具体来说，药效团定义了几种不同的非锌（II）配位小分子化学型重叠之间的分离，使设计和合成具有K(i) = 600 nM （+/- 100 nM）的新结构杂化物成为可能。(C) 2009年Elsevier Ltd.出版
Botulinum neurotoxins, responsible for the neuroparalytic syndrome botulism, are the deadliest of known biological toxins. The work described in this study was based on a three-zone pharmacophore model for botulinum neurotoxin serotype A light chain inhibition. Specifically, the pharmacophore defined a separation between the overlaps of several different, non-zinc(II)-coordinating small molecule chemotypes, enabling the design and synthesis of a new structural hybrid possessing a K(i) = 600 nM (+/- 100 nM). (C) 2009 Published by Elsevier Ltd.