title: Chirality holds the key for potent inhibition of the botulinum neurotoxin serotype a protease.
abstract: Botulinum neurotoxin serotype A (BoNT/A) is the most toxic protein known to man and also a bioterrorism agent. As defined by our previous research targeting the etiological agent responsible for BoNT/A intoxication, a protease, we now report on the asymmetric synthesis of four new BoNT/A inhibitors; the most potent of this series is roughly 2-fold more active than the best small molecule inhibitor currently known.
authors.affiliation: Department of Chemistry, The Skaggs Institute for Chemical Biology and Worm Institute of Research and Medicine (WIRM), The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.
authors.forename: G Neil
authors.initials: GN
authors.lastname: Stowe
authors.forename: Peter
authors.initials: P
authors.lastname: Silhár
authors.forename: Mark S
authors.initials: MS
authors.lastname: Hixon
authors.forename: Nicholas R
authors.initials: NR
authors.lastname: Silvaggi
authors.forename: Karen N
authors.initials: KN
authors.lastname: Allen
authors.forename: Scott T
authors.initials: ST
authors.lastname: Moe
authors.forename: Alan R
authors.initials: AR
authors.lastname: Jacobson
authors.forename: Joseph T
authors.initials: JT
authors.lastname: Barbieri
authors.forename: Kim D
authors.initials: KD
authors.lastname: Janda
mesh_terms: D019274:Botulinum Toxins, Type A / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000633:toxicity*; D002384:Catalysis; D003013:Clostridium / Q000737:chemistry*; D018360:Crystallography, X-Ray; D006801:Humans; D006877:Hydroxamic Acids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D009498:Neurotoxins / Q000037:antagonists & inhibitors*; D011480:Protease Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D006877:Hydroxamic Acids; D009498:Neurotoxins; D011480:Protease Inhibitors; D019274:Botulinum Toxins, Type A