Substrate-based design of the first class of angiotensin-converting enzyme-related carboxypeptidase (ACE2) inhibitors.

Journal of the American Chemical Society ·Vol. 124 ·No. 40 ·2002-10-09 ·Pages 11852-3

Dales NA, Gould AE, Brown JA, Calderwood EF, Guan B, Minor CA, Gavin JM, Hales P, Kaushik VK, Stewart M, Tummino PJ, Vickers CS, Ocain TD, Patane MA

Abstract

Angiotensin-converting enzyme-related carboxypeptidase (ACE2) is a recently identified zinc metalloprotease with carboxypeptidase activity that was identified using our genomics platform. We implemented a rational design approach to identify potent and selective ACE2 inhibitors. To this end, picomolar inhibitors of ACE2 were designed and synthesized.

MeSH Terms

Angiotensin-Converting Enzyme 2 Angiotensin-Converting Enzyme Inhibitors/chemical synthesis,chemistry,pharmacology Carboxypeptidases/antagonists & inhibitors Catalysis Drug Design Imidazoles/chemical synthesis,chemistry,pharmacology Peptidyl-Dipeptidase A Protein Structure, Tertiary Structure-Activity Relationship Succinates/chemical synthesis,chemistry,pharmacology

Chemicals

Angiotensin-Converting Enzyme Inhibitors Imidazoles Succinates benzylsuccinic acid Carboxypeptidases Peptidyl-Dipeptidase A Angiotensin-Converting Enzyme 2

Authors & Affiliations

14 authors, click to expand affiliations / ORCID

Dales Natalie A

Millennium Pharmaceuticals, Inc., 75 Sidney Street, Cambridge, MA 02139, USA.

Gould Alexandra E

Brown James A

Calderwood Emily F

Guan Bing

Minor Charles A

Gavin James M

Hales Paul

Kaushik Virendar K

Stewart Michael

Tummino Peter J

Vickers Chad S

Ocain Timothy D

Patane Michael A

Article Info

Journal

Journal of the American Chemical Society

Abbr.

J Am Chem Soc

ISSN

0002-7863

DOI

10.1021/ja0277226

Published

2002-10-09

Pages

11852-3

Language

English

Region

United States

NLM ID

7503056

Subset

External Links

PubMed source DOI: 10.1021/ja0277226 View journal details

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Substrate-based design of the first class of angiotensin-converting enzyme-related carboxypeptidase (ACE2) inhibitors.

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