In Vitro and In Silico Studies on Angiotensin I-Converting Enzyme Inhibitory Peptides Found in Hydrophobic Domains of Porcine Elastin

Overview

Journal Molecules

Publisher MDPI

Specialty Biology

Date 2023 Apr 28

PMID 37110571

Authors

Toshiya Hatakenaka

Tamaki Kato

Kouji Okamoto

Affiliations

Soon will be listed here.

Abstract

One of the most striking aspects of the primary structure in the hydrophobic domains of the tropoelastin molecule is the occurrence of the VAPGVG repeating sequence. Since the N-terminal tripeptide VAP of VAPGVG showed a potent ACE inhibitory activity, the ACE inhibitory activity of various derivatives of VAP was examined in vitro. The results showed that VAP derivative peptides VLP, VGP, VSP, GAP, LSP, and TRP exhibited potent ACE inhibitory activities, while the non-derivative peptide APG showed only weak activity. In in silico studies, the docking score S value showed that VAP derivative peptides VLP, VGP, VSP, LSP, and TRP had stronger docking interactions than APG. Molecular docking in the ACE active pocket showed that TRP, the most potent ACE inhibitory peptide among the VAP derivatives, had a larger number of interactions with ACE residues in comparison with APG and that the TRP molecule appeared to spread widely in the ACE pocket, while the APG molecule appeared to spread closely. Differences in molecular spread may be a reason why TRP exhibits more potent ACE inhibitory activity than APG. The results suggest that the number and strength of interactions between the peptide and ACE are important for the ACE- inhibitory potency of the peptide.

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References

Senior R, Griffin G, Mecham R . Chemotactic responses of fibroblasts to tropoelastin and elastin-derived peptides. J Clin Invest. 1982; 70(3):614-8. PMC: 370263. DOI: 10.1172/jci110654. View

Wang C, Tu M, Wu D, Chen H, Chen C, Wang Z . Identification of an ACE-Inhibitory Peptide from Walnut Protein and Its Evaluation of the Inhibitory Mechanism. Int J Mol Sci. 2018; 19(4). PMC: 5979345. DOI: 10.3390/ijms19041156. View

Zhang Q, Song C, Zhao J, Shi X, Sun M, Liu J . Separation and Characterization of Antioxidative and Angiotensin Converting Enzyme Inhibitory Peptide from Jellyfish Gonad Hydrolysate. Molecules. 2018; 23(1). PMC: 6017638. DOI: 10.3390/molecules23010094. View

Clark A, Labute P . 2D depiction of protein-ligand complexes. J Chem Inf Model. 2007; 47(5):1933-44. DOI: 10.1021/ci7001473. View

Nakamura Y, Yamamoto N, Sakai K, Okubo A, Yamazaki S, Takano T . Purification and characterization of angiotensin I-converting enzyme inhibitors from sour milk. J Dairy Sci. 1995; 78(4):777-83. DOI: 10.3168/jds.S0022-0302(95)76689-9. View

Nakano D, Ogura K, Miyakoshi M, Ishii F, Kawanishi H, Kurumazuka D . Antihypertensive effect of angiotensin I-converting enzyme inhibitory peptides from a sesame protein hydrolysate in spontaneously hypertensive rats. Biosci Biotechnol Biochem. 2006; 70(5):1118-26. DOI: 10.1271/bbb.70.1118. View

Gao X, Li X, Yan P, Sun R, Kan G, Zhou Y . Identification and Functional Mechanism of Novel Angiotensin I Converting Enzyme Inhibitory Dipeptides from Cultured in Shrimp Processing Waste Medium. Biomed Res Int. 2018; 2018:5089270. PMC: 5964570. DOI: 10.1155/2018/5089270. View

Isidro-Llobet A, Alvarez M, Albericio F . Amino acid-protecting groups. Chem Rev. 2009; 109(6):2455-504. DOI: 10.1021/cr800323s. View

Wu J, Aluko R, Nakai S . Structural requirements of Angiotensin I-converting enzyme inhibitory peptides: quantitative structure-activity relationship study of di- and tripeptides. J Agric Food Chem. 2006; 54(3):732-8. DOI: 10.1021/jf051263l. View

10.

Vukic V, Vukic D, Milanovic S, Ilicic M, Kanuric K, Johnson M . In silico identification of milk antihypertensive di- and tripeptides involved in angiotensin I-converting enzyme inhibitory activity. Nutr Res. 2017; 46:22-30. DOI: 10.1016/j.nutres.2017.07.009. View

11.

Matsuura K, Ota J, Fujita S, Shiomi Y, Inaba H . Construction of Ribonuclease-Decorated Artificial Virus-like Capsid by Peptide Self-assembly. J Org Chem. 2019; 85(3):1668-1673. DOI: 10.1021/acs.joc.9b02295. View

12.

Yang Y, Mai D, Li S, Morris M, Olsen B . Tuning Selective Transport of Biomolecules through Site-Mutated Nucleoporin-like Protein (NLP) Hydrogels. Biomacromolecules. 2021; 22(2):289-298. DOI: 10.1021/acs.biomac.0c01083. View

13.

Yang G, Qin S, Li W . Purification and characterization of a novel angiotensin I-converting enzyme-inhibitory peptide derived from Alaska pollack skins. J Food Sci. 2021; 86(6):2457-2467. DOI: 10.1111/1750-3841.15754. View

14.

Sobocinska M, Gieldon A, Fichna J, Kamysz E . 1-Substituted sialorphin analogues-synthesis, molecular modelling and in vitro effect on enkephalins degradation by NEP. Amino Acids. 2019; 51(8):1201-1207. DOI: 10.1007/s00726-019-02760-z. View

15.

Yu Z, Wu S, Zhao W, Ding L, Shiuan D, Chen F . Identification and the molecular mechanism of a novel myosin-derived ACE inhibitory peptide. Food Funct. 2017; 9(1):364-370. DOI: 10.1039/c7fo01558e. View

16.

Byun H, Kim S . Structure and activity of angiotensin I converting enzyme inhibitory peptides derived from Alaskan pollack skin. J Biochem Mol Biol. 2002; 35(2):239-43. DOI: 10.5483/bmbrep.2002.35.2.239. View

17.

Jiang S, Xue D, Zhang Z, Shan K, Ke W, Zhang M . Effect of Sous-vide cooking on the quality and digestion characteristics of braised pork. Food Chem. 2021; 375:131683. DOI: 10.1016/j.foodchem.2021.131683. View

18.

Xu Z, Wu C, Sun-Waterhouse D, Zhao T, Waterhouse G, Zhao M . Identification of post-digestion angiotensin-I converting enzyme (ACE) inhibitory peptides from soybean protein Isolate: Their production conditions and in silico molecular docking with ACE. Food Chem. 2020; 345:128855. DOI: 10.1016/j.foodchem.2020.128855. View

19.

Tu M, Wang C, Chen C, Zhang R, Liu H, Lu W . Identification of a novel ACE-inhibitory peptide from casein and evaluation of the inhibitory mechanisms. Food Chem. 2018; 256:98-104. DOI: 10.1016/j.foodchem.2018.02.107. View

20.

Wood R . Bronchospasm and cough as adverse reactions to the ACE inhibitors captopril, enalapril and lisinopril. A controlled retrospective cohort study. Br J Clin Pharmacol. 1995; 39(3):265-70. PMC: 1365002. DOI: 10.1111/j.1365-2125.1995.tb04447.x. View