The Synthesis And Properties Of Similar ACE Inhibitory Peptides

Hypertension, a common worldwide cardiovascular disease, has become an increasinglyserious medical and public health issue. Angiotensin I-converting enzyme plays an importantphysiological role in the regulation of blood pressure by virtue of the rennin angiotensinsystem. In addition, ACE can inactivate bradykinin, resulting in an increase of blood pressure.ACE inhibitory peptides can inhibit ACE activity by bonding with the active center of ACE,which result in lowering of the blood pressure. With the advantages in the treat ofhypertension such as better curative effect, non-toxic side effects, and no influence of regularblood pressure, ACE inhibitory peptides have become the hotspots of present research ontreat hypertension and medical research. The research on structure-activity relationship willprovide supports for the design and selection of such drugs and make a positive significancein treatment of hypertension and human health.This research was carried out on the basis of the structure characteristics of ACE inhibitorypeptides and for the purpose to study quantitative structure-activity relationship of ACEinhibitory peptides. First of all, two peptides, Lys-Val-Leu-Pro-Val-Pro (KVLPVP) andTyr-Lys-Ser-Phe-Ile-Lys-Gly-Tyr-Pro-Val-Met (YKSFIKGYPVM), have been proved withACE inhibit activity were selected as control system, and their17mimic peptides wasdesigned namely KVLPVF, KVLPRF, KVLPAF, KVLPVY, KVLPHY, KVLPVW,YKSFIKGYPV, YKSFIKGYP, YKSFIKGY, SFIKGYPV, FIKGYPVP, FIKGYPV, IKGYPV,YKSFIKGYPVA, YKVFIKGYPVAF, YKSFIKGYPSAFF, and YKSFIKGYPVAPVF. Thecontrol peptides and their mimic peptides were synthesized by Fmoc solid-phase synthesis,and the same method for the synthesis of a contrast peptide LKVGVGQY whose structure notsimilar to the structure characteristics of ACE inhibitory peptide. The purification andpreparation of synthetic products were carried out by using RP-HPLC and characterizationsof products were carried out by using ESI-MS.ACE inhibit activity of peptides was detected by RP-HPLC method in vitro. The resultsobtained showed that the ACE inhibitory activity of all KVLPVP mimic peptides wasincreased by4.53%-12.40%, which suggested that activity of peptides could be improved byaromatic amino acid Phe, Tyr and Trp, hydrophobic amino acid Val and Phe, and chargedamino acid Arg and His at C-end of peptides. As the shorten of YKSFIKGYPVM length namely remove C-end or the N-end amino acid residues of peptide, the overall ACE activityinhibit rate of peptides was reduced from97.19%to60.65%, which demonstrated that thelength of peptide, with the similar amino acid sequence, had certain effect on its ACE inhibitactivity. Thus it can be seen that ACE inhibitory activity was reduced as the shortening ofpeptide length. Of the mimic YKSFIKGYPVM peptides, ACE inhibitory activity ofYKSFIKGYPVA, YKSFIKGYP, YKSFIKGY, and FIKGYPVP are higher than the others, theanalysis results of ACE activity inhibit rate of peptides indicate that their activity wereincreased or decreased when Pro at different location of C-end.