Substrate-based Design of the First Class of Angiotensin-Converting Enzyme-Related Carboxypeptidase (ACE2) Inhibitors

J Am Chem Soc. 2002 Oct 9;124(40):11852-3. doi: 10.1021/ja0277226.

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

Substances

  • Angiotensin-Converting Enzyme Inhibitors
  • Imidazoles
  • Succinates
  • benzylsuccinic acid
  • Carboxypeptidases
  • Peptidyl-Dipeptidase A
  • angiotensin converting enzyme 2