In vitro and in silico studies of novel synthetic ACE-inhibitory peptides derived from Saccharomyces cerevisiae protein hydrolysate

• Published in: Bioorganic chemistry 2019-06, Vol.87, p.647-654
• Main Authors: Mirzaei, Mahta, Mirdamadi, Saeed, Safavi, Maliheh, Hadizadeh, Mahnaz
• Format: Article
• Language: English
• Subjects: ACE inhibitory activity; Saccharomyces cerevisiae; Structure-function; Synthetic peptides
• ISSN: 0045-2068; 1090-2120
• DOI: 10.1016/j.bioorg.2019.03.057

[Display omitted] •Four peptide analogues of YR-10 (YGKPVAVPAR) were synthesized.•Pro replacement with His led to increase in ACE-inhibitory activity.•Simulated intestinal digestion of YR-10 led to reduction in ACE-inhibitory activity.•The best ACE-inhibitory activity and docking poses obtained for YHR-10 (YGKPVAVHAR). The structure-function relation of YR-10 (YGKPVAVPAR) was investigated by synthesizing four structural analogs of that including YHR-10 (YGKHVAVHAR), GA-8 (GKPVAVPA), GHA-8 (GKHVAVHA), and PAR-3 (PAR). GA-8 (GKPVAVPA) was synthesized on the basis of simulated enzymatic gastrointestinal digestion performed by bioinformatics tools (expasy-peptide cutter). This study explains the molecular mechanisms for the interaction of synthetic peptides with ACE. The IC50 values of each were 139.554 ± 2.3, 61.91 ± 1.2, 463.230 ± 3.56, 135.135 ± 2.1, 514.024 ± 5.86 µM, respectively. Results indicated that Pro replacement with His in YR-10 and GA-8 increased ACE inhibitory activity respectively, by 55.63% and 70.82%. Removal of Tyr and Arg from respectively N and C terminal positions of YR-10, following in silico simulated gastrointestinal digestion caused the 3.31 fold decrease in ACE inhibitory activity. YHR-10 showed the best docking poses, and GHA-8 exhibited interaction with Zn2+. Lineweaver–Burk plots of most active peptides suggest that they act as noncompetitive inhibitors against ACE.