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

ABSTRACT: 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.

SUBMITTER: McAllister LA

PROVIDER: S-EPMC2529174 | biostudies-literature | 2006 Apr

REPOSITORIES: biostudies-literature

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

McAllister Laura A LA Hixon Mark S MS Kennedy Jack P JP Dickerson Tobin J TJ Janda Kim D KD

Journal of the American Chemical Society 20060401 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 m ...[more]

PMID: 16568962

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