Microwave-assisted Solid-phase Synthesis, Biological Evaluation and Molecular Docking of Angiotensin I-converting Enzyme Inhibitors

作     者：SUN Yang1, HUANG Da-wei1, LI Xiao-hui1, HU Jian-en2 and XIU Zhi-long1 1. School of Life Science and Biotechnology, Dalian University of Technology, Dalian 116024, P. R. China 2. School of Food Engineering, Dalian Ocean University, Dalian 116023, P. R. China 

作者机构：School of Life Science and Biotechnology Dalian University of Technology Dalian 116024 School of Food Engineering Dalian Ocean University Dalian 116023 

出 版 物：《Chemical Research in Chinese Universities》 (高等学校化学研究（英文版）)

年 卷 期：2012年第28卷第1期

页      面：108-113页

核心收录：

学科分类：1007[医学-药学(可授医学、理学学位)] 100701[医学-药物化学] 10[医学] 

基　　金：Supported by the National High Technology Research and Development Program of China(No.2006AA10Z331) 

主　　题：Angiotensin I-converting enzyme Peptide inhibitor Molecular docking Microwave-assisted solid-phasesynthesis 

摘      要：Short peptides based on the tripeptides, Leu-Arg-Pro and Leu-Lys-Pro, were synthesized by microwave assisted solid-phase synthesis method, in order to make a search for potential inhibitors for angiotensin I-converting enzyme（ACE） with minimum side effects in the treatment of hypertension. One peptide with the sequence Leu-Arg-Pro-Phe-Phe shows the strongest inhibition towards ACE with an IC50 value of 0.26 μmol/L in vitro. The study of structure-activity relationship shows that the introduction of a bulky group into the N-terminal of this series of inhibitors may enlarge steric hindrance, resulting in the poor inhibitory activity towards ACE. The inhibitory activity decreased in turn when L-Pro, D-Pro or Ac6c was at the C-terminal respectively. The binding interaction between each of these inhibitors and testicular ACE（tACE） was performed by molecular docking. The results suggest that Leu-Arg-Pro-Phe-Phe mainly occupied the S1 subsite of tACE, and made contact with tACE via seven H-bonds. It appeared that the site on the peptide that bound with tACE was influenced by the configuration of the amino acid, L or D-form, at the C-terminal of the peptide.