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Publication . Article . 2019

Design and evaluation of four novel tripeptides as potent angiotensin converting enzyme (ACE) inhibitors with anti-hypertension activity

Bingjun Qian; Chongchong Tian; Huo Jianghua; Zhiwen Ding; Ran Xu; Juan Zhu; Lili Yu; +1 Authors
Closed Access
Published: 01 Dec 2019 Journal: Peptides, volume 122, page 170,171 (issn: 0196-9781, Copyright policy )
Publisher: Elsevier BV
Abstract

The current study investigated the angiotensin-converting enzyme (ACE) inhibitory activity of 4 synthetic tripeptides. All the peptides showed enzyme inhibitory activity, especially two promising ones, TTP (Thea-Thea-Pro) and gAgAP (GABA-GABA-Pro), with IC50 values of 0.92 and 3.4 μmol/L, respectively. Enzyme inhibition kinetics determined by Lineweaver-Burk plots revealed that TTP and gAgAP were competitive inhibitors with Ki values of 0.87 and 3.12 μmol/L, respectively. Molecular docking experiments confirmed that the higher inhibitory potency of TTP and gAgAP might be attributed to the formation of several critical hydrogen bonds with the active site residues in ACE. We further demonstrated that TTP and gAgAP initiated a rapid and significant decrease in systolic blood pressure (SBP) in spontaneously hypertensive rats (SHRs). TTP treatment lowered SBP to the same extent as captopril, although the duration of anti-hypertensive effect was shorter in TTP group than that observed in captopril group. Moreover, the transcription levels of angiotensin II receptor type 1 (agtr1) and miR-132/-212 were downregulated in SHRs after administration of TTP and gAgAP. In particular, TTP treatment caused a comparable reduction of agtr1 levels compared to captopril treatment, while miR-132/212 expression was significantly decreased. These results showed that compound TTP might be served as a potential antihypertensive candidate.

Subjects by Vocabulary

Microsoft Academic Graph classification: Angiotensin-converting enzyme biology.protein biology Inhibitory postsynaptic potential Active site Blood pressure Pharmacology Angiotensin II receptor type 1 Tripeptide Captopril medicine.drug medicine Chemistry Enzyme chemistry.chemical_classification

Medical Subject Headings: hemic and lymphatic diseases respiratory system

Subjects

Cellular and Molecular Neuroscience, Endocrinology, Physiology, Biochemistry

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