Solid-phase synthesis of hydroxyethylamine angiotensin analogues

Peptides. 1997;18(4):505-12. doi: 10.1016/s0196-9781(96)00331-2.

Abstract

Three hydroxyethylamine analogues of angiotensins II, III, and IV were prepared by solid-phase methods. The resin-bound peptide was alkylated with the iodomethylketone derivative of the N-terminal amino acid, followed by reduction to the alcohol using sodium borohydride. The iodomethylketones can be made in good yields from commercially available N-protected amino acids. The compounds were evaluated for their ability to displace labeled angiotensins from bovine adrenal membranes, and their metabolic stability tested in kidney homogenates and aminopeptidase M preparations. The hydroxyethylamine amide bond replacement reduced the affinity of the analogues; however, they were substantially more stable to enzymatic degradation.

MeSH terms

  • Adrenal Glands / drug effects
  • Adrenal Glands / ultrastructure
  • Amino Acids / chemistry*
  • Aminopeptidases / metabolism
  • Angiotensin II / analogs & derivatives*
  • Angiotensin II / chemical synthesis
  • Angiotensin II / pharmacology
  • Animals
  • Automation
  • Binding, Competitive
  • Cattle
  • Hydrocarbons, Halogenated / chemistry*
  • Ketones / chemistry*
  • Kidney / drug effects
  • Kidney / ultrastructure
  • Male
  • Membranes / drug effects
  • Methionyl Aminopeptidases
  • Rats
  • Rats, Sprague-Dawley
  • Structure-Activity Relationship

Substances

  • Amino Acids
  • Hydrocarbons, Halogenated
  • Ketones
  • Angiotensin II
  • Aminopeptidases
  • Methionyl Aminopeptidases