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

高等学校化学研究 ›› 2012, Vol. 28 ›› Issue (1): 108-113.

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

SUN Yang¹, HUANG Da-wei¹, LI Xiao-hui^1*, HU Jian-en², 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

收稿日期:2011-03-01 修回日期:2011-07-05 出版日期:2012-01-25 发布日期:2011-12-27
基金资助:
Supported by the National High Technology Research and Development Program of China(No.2006AA10Z331).

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

SUN Yang¹, HUANG Da-wei¹, LI Xiao-hui^1*, HU Jian-en², 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

Received:2011-03-01 Revised:2011-07-05 Online:2012-01-25 Published:2011-12-27
Contact: Xiao-Hui LI E-mail:lxhxh@dlut.edu.cn
Supported by:
Supported by the National High Technology Research and Development Program of China(No.2006AA10Z331).

摘要/Abstract

摘要： Short peptides based on the tripeptides, Leu-Arg-Pro and Leu-Lys-Pro, were synthesized by microwaveassisted 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.

关键词: Angiotensin I-converting enzyme, Peptide inhibitor, Molecular docking, Microwave-assisted solid-phase synthesis

Abstract: Short peptides based on the tripeptides, Leu-Arg-Pro and Leu-Lys-Pro, were synthesized by microwaveassisted 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.

Key words: Angiotensin I-converting enzyme, Peptide inhibitor, Molecular docking, Microwave-assisted solid-phase synthesis

SUN Yang, HUANG Da-wei, LI Xiao-hui, HU Jian-en, XIU Zhi-long. Microwave-assisted Solid-phase Synthesis, Biological Evaluation and Molecular Docking of Angiotensin I-converting Enzyme Inhibitors[J]. 高等学校化学研究, 2012, 28(1): 108-113.

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

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

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