关于E环在(+)-阿里苏加辛A与乙酰胆碱酯酶结合中重要性的计算观点。
A computational view on the significance of E-ring in binding of (+)-arisugacin A to acetylcholinesterase.
作者信息
Al-Rashid Ziyad F, Hsung Richard P
机构信息
Alchemical Research, LLC, 260 East Wall Street, Bethlehem, PA 18018, USA.
Division of Pharmaceutical Sciences, School of Pharmacy, and Department of Chemistry, University of Wisconsin, Madison, WI 53705, USA.
出版信息
Bioorg Med Chem Lett. 2015 Nov 1;25(21):4848-4853. doi: 10.1016/j.bmcl.2015.06.047. Epub 2015 Jun 27.
Abstract
A computational docking study of a series of de novo structural analogs of the highly potent, non-nitrogen containing, acetylcholinesterase inhibitor (+)-arisugacin A is presented. In direct comparison to the recently reported X-ray single-crystal structure of (+)-territrem B bound hAChE, the modeling suggests that there is a unique conformational preference for the E-ring that is responsible for the superior inhibitory activity of (+)-arisugacin A against hAChE relative to (+)-territrem B, and that substitutions on the E-ring also play an important role in the protein-ligand interaction.
摘要
本文介绍了一系列高效、不含氮的乙酰胆碱酯酶抑制剂（+）-阿瑞苏加辛A的从头结构类似物的计算对接研究。与最近报道的（+）-震颤毒素B与hAChE结合的X射线单晶结构直接比较，模型表明E环存在独特的构象偏好，这是（+）-阿瑞苏加辛A相对于（+）-震颤毒素B对hAChE具有优异抑制活性的原因，并且E环上的取代在蛋白质-配体相互作用中也起着重要作用。
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