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Synthetic Tripeptides as Inhibitors of Angiotensin I‐Converting Enzyme

Shruthi Pai, P. (2009) Synthetic Tripeptides as Inhibitors of Angiotensin I‐Converting Enzyme. [Student Project Report]

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This Dissertation / Report is the outcome of investigation carried out by the creator(s) / author(s) at the department/division of Central Food Technological Research Institute (CFTRI), Mysore mentioned below in this page.

Item Type: Student Project Report
Additional Information: Interest has recently been directed to the identification, isolation and purification of angiotensin converting enzyme (ACE) inhibitor peptides from enzymatic hydrolysates of food proteins. ACE inhibitor peptides derived from daily dietary food proteins are useful in the development of a novel functional additive and present a healthier and natural alternative to synthetic ACE inhibitor drugs. Recently a tripeptide, isoleucyl‐glutamyl‐tyrosine (IEY) isolated from an enzymatic hydrolysate of arachin, the major storage protein of peanut (Arachis hypogaea) was shown to be potent competitive inhibitor of ACE. The mechanism by which this tripeptide inhibits ACE is yet unknown. Structural analogs of this peptide were used to understand the structural features that contribute to the ACE inhibition. The biologically active tripeptides isoleucyl‐lysyl‐tyrosine (IKY), isoleucyl‐lysyl‐tryptophan (IKW) and isoleucyl‐lysyl‐proline (IKP) were designed and their inhibitory properties studied. The illustration to their interaction with the active site of ACE was maintained as a function of the structure and specific conformations adopted by the peptide in the microenvironment to bring about the inhibitory activity. The synthesized peptides were purified and the inhibitory kinetics against a partially purified porcine kidney ACE investigated. The purity of the peptides was established by amino acid analysis and RP‐HPLC. Computer aided modeling using ArgusLab was used to predict their binding to ACE. The relation between the experimentally obtained binding energies and the binding energies calculated in silico were established. The peptide, IKP emerged as the most potent peptide with respect to the binding and inhibitor efficiency towards ACE. The susceptibility of the peptides to pancreatin digestion of the peptides led the way to designing a protease resistant peptide where L‐isomer of lysine was replaced by a D‐isomer. This however, showed that although the peptide was resistant, inhibitory potency was very low. Further, a fluorescent resonance energy transfer (FRET) peptide was synthesized as a substrate for ACE, which emerged as a sensitive substrate for assaying ACE and its inhibitors.
Uncontrolled Keywords: angiotensin converting enzyme inhibitor peptides enzymatic hydrolysates food proteins
Subjects: 600 Technology > 08 Food technology > 16 Nutritive value > 03 Proteins
Divisions: Protein Chemistry and Technology
Depositing User: Food Sci. & Technol. Information Services
Date Deposited: 22 Sep 2009 06:42
Last Modified: 28 Dec 2011 10:11
URI: http://ir.cftri.com/id/eprint/9180

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