Seki Hajime, Xue Song, Hixon Mark S, Pellett Sabine, Remes Marek, Johnson Eric A, Janda Kim D
Departments of Chemistry and Immunology and Microbial Sciences, The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Chem Commun (Camb). 2015 Apr 11;51(28):6226-9. doi: 10.1039/c5cc00677e.
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.
Dyngo-4a™已被发现是一种通过抑制发动蛋白来抑制肉毒杆菌毒素A（BoNT/A）神经毒性的内吞抑制剂。在此，我们证明该分子对BoNT/A具有一种先前未被认识到的双重活性，即抑制发动蛋白-蛋白酶。为了确定这种双重活性的重要性，我们描述了Dyngo-4a对BoNT/A金属蛋白酶抑制作用的详细动力学分析以及细胞和动物毒性研究。所呈现的研究是对抗BoNT/A中毒的首个多药理学方法。
