Superactivation of the botulinum neurotoxin serotype a light chain metalloprotease: A new wrinkle in botulinum neurotoxin

被引：18
作者：
McAllister, LA
Hixon, MS
Kennedy, JP
Dickerson, TJ
Janda, KD
机构：
[1] Skaggs Inst Chem Biol, Dept Chem, La Jolla, CA 92037 USA
[2] Scripps Res Inst, Worm Inst Res & Med, La Jolla, CA 92037 USA
来源：
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY | 2006年 / 128卷 / 13期
关键词：
D O I：
10.1021/ja057699z
中图分类号：
O6 [化学];
学科分类号：
0703 ;
摘要：
Small molecules based upon a 2-acylguanidine-5-phenyl thiophene scaffold that can activate the light chain metalloprotease of botulinum neurotoxin serotype A (BoNT LC/A) by an apparent reduction in Km are reported. On the basis of structure-activity relationships and the activation profile, one or more molecules of activator specifically bind to a defined site on the toxin, causing the observed rate enhancement. With the ever-growing clinical uses of BoNT, compounds such as those reported here may provide a method for combating the emerging adaptive immune responses to BoNT. Copyright © 2006 American Chemical Society.
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页码：4176 / 4177
页数：2
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