A型肉毒杆菌神经毒素抑制剂：小分子巯基乙酰胺类似物
Botulinum neurotoxin serotype A inhibitors: small-molecule mercaptoacetamide analogs.
作者信息
Moe Scott T, Thompson Andrew B, Smith Genessa M, Fredenburg Ross A, Stein Ross L, Jacobson Alan R
机构信息
Absolute Science, Inc., Lexington, MA 02421, United States.
出版信息
Bioorg Med Chem. 2009 Apr 15;17(8):3072-9. doi: 10.1016/j.bmc.2009.03.013. Epub 2009 Mar 14.
Abstract
Botulinum neurotoxin elicits its paralytic activity through a zinc-dependant metalloprotease that cleaves proteins involved in neurotransmitter release. Currently, no drugs are available to reverse the effects of botulinum intoxication. Herein we report the design of a novel series of mercaptoacetamide small-molecule inhibitors active against botulinum neurotoxin serotype A. These analogs show low micromolar inhibitory activity against the isolated enzyme. Structure-activity relationship studies for a series of mercaptoacetamide analogs of 5-amino-3-phenylpyrazole reveal components essential for potent inhibitory activity.
摘要
肉毒杆菌神经毒素通过一种依赖锌的金属蛋白酶引发其麻痹活性，该酶可切割参与神经递质释放的蛋白质。目前，尚无药物可逆转肉毒杆菌中毒的影响。在此，我们报告了一系列新型巯基乙酰胺小分子抑制剂的设计，这些抑制剂对A型肉毒杆菌神经毒素具有活性。这些类似物对分离出的酶显示出低微摩尔级的抑制活性。对一系列5-氨基-3-苯基吡唑的巯基乙酰胺类似物的构效关系研究揭示了强效抑制活性所必需的成分。
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