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2006:
McAllister Laura A; Hixon Mark S; Kennedy Jack P; Dickerson Tobin J; Janda Kim D
Superactivation of the botulinum neurotoxin serotype A light chain metalloprotease: a new wrinkle in botulinum neurotoxin.
Journal of the American Chemical Society 2006;
128(
13):.
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.
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