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乙酰胆碱酯酶：用于治疗阿尔茨海默病的抗胆碱酯酶药物基于结构的药物设计的多方面靶点。

Acetylcholinesterase: a multifaceted target for structure-based drug design of anticholinesterase agents for the treatment of Alzheimer's disease.

作者信息

Greenblatt Harry M, Dvir Hay, Silman Israel, Sussman Joel L

机构信息

Department of Structural Biology, Weizmann Institute of Science, Rehovot, Israel.

出版信息

J Mol Neurosci. 2003;20(3):369-83. doi: 10.1385/JMN:20:3:369.

DOI:10.1385/JMN:20:3:369
PMID:14501022
Abstract

The structure of Torpedo californica acetylcholinesterase is examined in complex with several inhibitors that are either in use or under development for treating Alzheimer's disease. The noncovalent inhibitors vary greatly in their structures and bind to different sites of the enzyme, offering many different starting points for future drug design.

摘要

研究了加州电鳐乙酰胆碱酯酶与几种用于治疗阿尔茨海默病或正在研发的抑制剂的复合物结构。这些非共价抑制剂的结构差异很大，并且与该酶的不同位点结合，为未来药物设计提供了许多不同的起点。

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J Am Chem Soc. 2003 Jan 15;125(2):363-73. doi: 10.1021/ja021111w.
2
X-ray structures of Torpedo californica acetylcholinesterase complexed with (+)-huperzine A and (-)-huperzine B: structural evidence for an active site rearrangement.与（+）-石杉碱甲和（-）-石杉碱乙复合的加州电鳐乙酰胆碱酯酶的X射线结构：活性位点重排的结构证据。
Biochemistry. 2002 Sep 3;41(35):10810-8. doi: 10.1021/bi020151+.
3
Restraint Stress Exacerbates Apoptosis in a 6-OHDA Animal Model of Parkinson Disease.
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4
Explainable machine learning predictions of dual-target compounds reveal characteristic structural features.可解释机器学习对双靶化合物预测的结果揭示了其特征结构特征。
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5
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4
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6
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8
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Mol Pharmacol. 2000 Feb;57(2):409-17.