肉毒杆菌神经毒素 A 蛋白酶：天然产物外位抑制剂的发现。
Botulinum neurotoxin A protease: discovery of natural product exosite inhibitors.
机构信息
Department of Chemistry, and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.
出版信息
J Am Chem Soc. 2010 Mar 10;132(9):2868-9. doi: 10.1021/ja910761y.
Abstract
A new mechanistic class of BoNT/A zinc metalloprotease inhibitors, from Echinacea, exemplified by the natural product d-chicoric acid (I1) is disclosed. A detailed evaluation of chicoric acid's mechanism of inhibition reveals that the inhibitor binds to an exosite, displays noncompetitive partial inhibition, and is synergistic with a competitive active site inhibitor when used in combination. Other components found in Echinacea, I3 and I4, were also inhibitors of the protease.
摘要
本发明公开了一种新型的 BoNT/A 锌金属蛋白酶抑制剂的作用机制类别，来源于松果菊，以天然产物 d-菊苣酸（I1）为代表。详细评估菊苣酸的抑制机制表明，抑制剂与外位结合，表现出非竞争性部分抑制，与竞争性活性位点抑制剂联合使用时具有协同作用。在松果菊中发现的其他成分，即 I3 和 I4，也是蛋白酶的抑制剂。
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