Department of Chemistry, and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.
J Am Chem Soc. 2010 Mar 10;132(9):2868-9. doi: 10.1021/ja910761y.
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.
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。