Toward the discovery of dual inhibitors for botulinum neurotoxin A: concomitant targeting of endocytosis and light chain protease activity. Issue 28 (11th March 2015)

• Record Type: Journal Article
• Authors: Seki, Hajime; Xue, Song; Hixon, Mark S.; Pellett, Sabine; Remes̆, Marek; Johnson, Eric A.; Janda, Kim D.
• Is Part Of: Chemical communications. Volume 51:Issue 28(2015)
• Page Start: 6226
• Page End: 6229
• Publication Date: 2015-03-11
• Subjects: Chemistry -- Periodicals; 540
• DOI: 10.1039/c5cc00677e
• Languages: English
• ISSNs: 1359-7345

Abstract

Abstract : A polypharmacological approach as a treatment for botulinum neurotoxin A intoxication is presented. Abstract : Dyngo-4a™ has been found to be an endocytic inhibitor of BoNT/A neurotoxicity through dynamin inhibition. Herein, we demonstrate this molecule to have a previously unrecognized dual activity against BoNT/A, dynamin–protease inhibition. To establish the importance of this dual activity, detailed kinetic analysis of Dyngo-4a's inhibition of BoNT/A metalloprotease as well as cellular and animal toxicity studies have been described. The research presented is the first polypharmacological approach to counteract BoNT/A intoxication.