Beta-homo-amino acid scan of angiotensin IV

J Med Chem. 2008 Apr 10;51(7):2291-6. doi: 10.1021/jm701490g. Epub 2008 Mar 15.

Abstract

Angiotensin IV, a metabolite of angiotensin II, inhibits the enzyme insulin regulated aminopeptidase or IRAP and also, although with lower potency, aminopeptidase-N (AP-N). When both beta (2)-homo amino acid- and beta (3)-homo amino acid substitutions were used, allowed the identification of H-( R)beta (2)hVal-Tyr-Ile-His-Pro-beta (3)hPhe-OH as a potent and stable Ang IV analog with high selectivity for IRAP versus AP-N and the AT1 receptor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Substitution
  • Amino Acids / chemistry*
  • Aminopeptidases / antagonists & inhibitors
  • Angiotensin II / analogs & derivatives*
  • Angiotensin II / chemical synthesis
  • Angiotensin II / chemistry
  • Angiotensin II / pharmacology
  • Animals
  • Binding Sites
  • CD13 Antigens / antagonists & inhibitors
  • CHO Cells
  • Cell Line
  • Cell Membrane / drug effects
  • Cricetinae
  • Cricetulus
  • Dose-Response Relationship, Drug
  • Enzyme Activation / drug effects
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology
  • Humans
  • Molecular Structure
  • Receptor, Angiotensin, Type 1 / drug effects
  • Structure-Activity Relationship

Substances

  • Amino Acids
  • Enzyme Inhibitors
  • Receptor, Angiotensin, Type 1
  • Angiotensin II
  • angiotensin II, des-Asp(1)-des-Arg(2)-Ile(5)-
  • Aminopeptidases
  • CD13 Antigens