Examination of α-exosite inhibitors against Botulinum neurotoxin A protease through structure-activity relationship studies of chicoric acid.
Examination of α-exosite inhibitors against Botulinum neurotoxin A protease through structure-activity relationship studies of chicoric acid.
复制标题
通过菊苣酸的结构-活性关系研究检查针对肉毒杆菌神经毒素 A 蛋白酶的 α-外位点抑制剂。
DOI：
10.1016/j.bmcl.2017.10.021
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发表时间：
2017
影响因子：
2.7
通讯作者：
Janda,Kim
中科院分区：
文献类型：
--
作者：
Xue,Song;Seki,Hajime;Remes,Marek;Šilhár,Peter;Janda,Kim
肉毒杆菌神经毒素（Botulinumneurotoxins，BoNT）是已知毒性最大的物质之一，目前还没有有效的治疗方法用于神经元内BoNT中毒。Chicoric acid（ChA）以前被报道为BoNT/A抑制剂，其结合酶的α-外位点。本文报道了一系列ChA衍生物的合成及其构效关系，揭示了ChA与BoNT/A之间的相互作用。此外，发现了几种基于ChA的抑制剂，其对BoNT/A具有改善的效力。
Botulinumneurotoxins (BoNT) are among the most toxic known substances and currently there are no effective treatments for intraneuronal BoNT intoxication. Chicoric acid (ChA) was previously reported as a BoNT/A inhibitor that binds to the enzyme’s α-exosite. Herein, we report the synthesis and structure-activity relationships (SARs) of a series of ChA derivatives, which revealed essential binding interactions between ChA and BoNT/A. Moreover, several ChA-based inhibitors with improved potency against the BoNT/A were discovered.