Solid-phase synthesis of hydroxyethylamine angiotensin analogues.
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.
Chambers
S L
SL
Department of Chemistry, Washington State University, Pullman 99164-6510, USA.
Ronald
R
R
Hanesworth
J M
JM
Kinder
D H
DH
Harding
J W
JW
D000311:Adrenal Glands / Q000187:drug effects / Q000648:ultrastructure; D000596:Amino Acids / Q000737:chemistry*; D000626:Aminopeptidases / Q000378:metabolism; D000804:Angiotensin II / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D000818:Animals; D001331:Automation; D001667:Binding, Competitive; D002417:Cattle; D006846:Hydrocarbons, Halogenated / Q000737:chemistry*; D007659:Ketones / Q000737:chemistry*; D007668:Kidney / Q000187:drug effects / Q000648:ultrastructure; D008297:Male; D008566:Membranes / Q000187:drug effects; D063208:Methionyl Aminopeptidases; D051381:Rats; D017207:Rats, Sprague-Dawley; D013329:Structure-Activity Relationship
D000596:Amino Acids; D006846:Hydrocarbons, Halogenated; D007659:Ketones; D000804:Angiotensin II; D000626:Aminopeptidases; D063208:Methionyl Aminopeptidases