McAllister Laura A, Hixon Mark S, Kennedy Jack P, Dickerson Tobin J, Janda Kim D
Department of Chemistry, The Skaggs Institute for Chemical Biology, La Jolla, California 92037, USA.
J Am Chem Soc. 2006 Apr 5;128(13):4176-7. doi: 10.1021/ja057699z.
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.
据报道，基于2-酰基胍-5-苯基噻吩支架的小分子能够通过明显降低米氏常数（Km）来激活A型肉毒杆菌神经毒素（BoNT LC/A）的轻链金属蛋白酶。基于构效关系和激活曲线，一种或多种激活剂分子特异性结合到毒素上的特定位点，从而导致观察到的速率增强。随着BoNT在临床上的应用不断增加，本文报道的这类化合物可能为对抗新出现的针对BoNT的适应性免疫反应提供一种方法。
