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Design of substrate-type ACE inhibitory pentapeptides with an antepenultimate C-terminal proline for efficient release of inhibitory activity

Paper ID Volume ID Publish Year Pages File Format Full-Text
3660 181 2012 6 PDF Available
Title
Design of substrate-type ACE inhibitory pentapeptides with an antepenultimate C-terminal proline for efficient release of inhibitory activity
Abstract

Much research has verified that tripeptides initiated with a branched-chain aliphatic amino acid residue and terminated with a proline have a strong antihypertensive activity in vivo. However, it is difficult to release from their precursor proteins that are orally administered. Based on the selectivity of angiotensin I-converting enzyme (ACE) on C-terminal dipeptides in its substrate, six pentapeptides with the same tripeptide IKP (as a model) at N-terminus including IKPVQ, IKPVA, IKPVK, IKPVR, IKPFR, and IKPHL were designed and chemically synthesized. It was shown that all the pentapeptides released IKP after ACE incubation. The release rate ranged from 23% (IKPHL) to 84.6% (IKPVR) as compared to the peptide sample before incubation. The in vitro digestion experiment demonstrated that all of the pentapeptides except IKPVA with a retention rate of 80.5% were resistant to pepsin hydrolysis but not to pancreatic hydrolysis. It should be noted that IKP could be released from IKPFR by pancreatin digestion. These results suggest that IKPVA and IKPFR potentially have a great antihypertensive effect in vivo. Furthermore, the dipeptides VA and FR described here may be widely used as linkers to help the release of the active peptides with proline at C-terminus from their protein precursors by ACE or gastrointestinal enzymes in human body.

► Design of substrate-type ACE inhibitory pentapeptides. ► Stability of the pentapeptides to ACE. ► Pro-Val and Pro-Phe peptide bond were susceptible to hydrolysis by ACE. ► Stability of the pentapeptides to gastrointestinal enzymes. ► IKPVA and IKPFR have the potential antihypertensive activity in vivo.

Keywords
Biomedical; Enzyme activity; Substrate inhibition; Food engineering; Angiotensin I-converting enzyme inhibitory peptide; Design
First Page Preview
Design of substrate-type ACE inhibitory pentapeptides with an antepenultimate C-terminal proline for efficient release of inhibitory activity
Publisher
Database: Elsevier - ScienceDirect
Journal: Biochemical Engineering Journal - Volume 60, 15 January 2012, Pages 50–55
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering