title: Botulinum neurotoxin serotype A inhibitors: small-molecule mercaptoacetamide analogs.
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.
authors.affiliation: Absolute Science, Inc., Lexington, MA 02421, United States.
authors.forename: Scott T
authors.initials: ST
authors.lastname: Moe
authors.forename: Andrew B
authors.initials: AB
authors.lastname: Thompson
authors.forename: Genessa M
authors.initials: GM
authors.lastname: Smith
authors.forename: Ross A
authors.initials: RA
authors.lastname: Fredenburg
authors.forename: Ross L
authors.initials: RL
authors.lastname: Stein
authors.forename: Alan R
authors.initials: AR
authors.lastname: Jacobson