Effect of peptide-based captopril analogues on angiotensin converting enzyme activity and peroxynitrite-mediated tyrosine nitration

Bhuyan, Bhaskar J and Mugesh, Govindasamy (2011) Effect of peptide-based captopril analogues on angiotensin converting enzyme activity and peroxynitrite-mediated tyrosine nitration. In: Organic and Biomolecular Chemistry, 9 (14). pp. 5185-5192.

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Abstract

Angiotensin converting enzyme (ACE) regulates the blood pressure by converting angiotensin I to angiotensin II and bradykinin to bradykinin 1-7. These two reactions elevate the blood pressure as angiotensin II and bradykinin are vasoconstrictory and vasodilatory hormones, respectively. Therefore, inhibition of ACE is an important strategy for the treatment of hypertension. The natural substrates of ACE, i.e., angiotensin II and bradykinin, contain a Pro-Phe motif near the site of hydrolysis. Therefore, there may be a Pro-Phe binding pocket at the active site of ACE, which may facilitate the substrate binding. In view of this, we have synthesized a series of thiol-and selenol-containing dipeptides and captopril analogues and studied their ACE inhibition activities. This study reveals that both the selenol or thiol moiety and proline residues are essential for ACE inhibition. Although the introduction of a Phe residue to captopril and its selenium analogue considerably reduces the inhibitory effect, there appears to be a Phe binding pocket at the active site of ACE.

Item Type:	Journal Article
Publication:	Organic and Biomolecular Chemistry
Publisher:	Royal Society of Chemistry
Additional Information:	Copyright of this article belongs to Royal Society of Chemistry.
Department/Centre:	Division of Chemical Sciences > Inorganic & Physical Chemistry
Date Deposited:	18 Jul 2011 08:36
Last Modified:	18 Jul 2011 08:36
URI:	http://eprints.iisc.ac.in/id/eprint/39086

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