Synthesis and molecular modeling of a lisinopril-tryptophan analogue inhibitor of angiotensin I-converting enzyme

Aloysius T Nchinda; Kelly Chibale; Pierre Redelinghuys; Edward D Sturrock

doi:10.1016/j.bmcl.2006.06.004

Synthesis and molecular modeling of a lisinopril-tryptophan analogue inhibitor of angiotensin I-converting enzyme

Bioorg Med Chem Lett. 2006 Sep 1;16(17):4616-9. doi: 10.1016/j.bmcl.2006.06.004. Epub 2006 Jun 19.

Authors

Aloysius T Nchinda¹, Kelly Chibale, Pierre Redelinghuys, Edward D Sturrock

Affiliation

¹ Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Observatory, South Africa.

PMID: 16784843
DOI: 10.1016/j.bmcl.2006.06.004

Abstract

With a view to developing a more C-domain-selective angiotensin I-converting enzyme (ACE)-inhibitor, a novel analogue of lisinopril has been synthesized which incorporates a bulky P(2)(') tryptophan functionality. This inhibitor demonstrated a significantly increased specificity for the C-domain as compared with lisinopril. Molecular docking revealed hydrophobic and hydrogen-bonding interactions with residues of the C-domain S(2)(') subsite.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Angiotensin-Converting Enzyme Inhibitors / chemical synthesis*
Angiotensin-Converting Enzyme Inhibitors / chemistry
Angiotensin-Converting Enzyme Inhibitors / pharmacology*
Binding Sites
Lisinopril / chemistry*
Models, Molecular
Molecular Structure
Peptidyl-Dipeptidase A / chemistry
Peptidyl-Dipeptidase A / metabolism
Tryptophan / analogs & derivatives
Tryptophan / chemical synthesis
Tryptophan / chemistry*

Substances

Angiotensin-Converting Enzyme Inhibitors
Tryptophan
Lisinopril
Peptidyl-Dipeptidase A