Beta-homo-amino acid scan of angiotensin IV.
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.
Lukaszuk
Aneta
A
Department of Organic Chemistry, Department of Molecular and Biochemical Pharmacology, Vrije Universiteit Brussel, Pleinlaan 2, 1050 Brussels, Belgium. alukaszu@vub.ac.be
Demaegdt
Heidi
H
Szemenyei
Erzsebet
E
Tóth
Géza
G
Tymecka
Dagmara
D
Misicka
Aleksandra
A
Karoyan
Philippe
P
Vanderheyden
Patrick
P
Vauquelin
Georges
G
Tourwé
Dirk
D
D019943:Amino Acid Substitution; D000596:Amino Acids / Q000737:chemistry*; D000626:Aminopeptidases / Q000037:antagonists & inhibitors; D000804:Angiotensin II / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D001665:Binding Sites; D018826:CD13 Antigens / Q000037:antagonists & inhibitors; D016466:CHO Cells; D002460:Cell Line; D002462:Cell Membrane / Q000187:drug effects; D006224:Cricetinae; D003412:Cricetulus; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D015394:Molecular Structure; D044140:Receptor, Angiotensin, Type 1 / Q000187:drug effects; D013329:Structure-Activity Relationship
D000596:Amino Acids; D004791:Enzyme Inhibitors; D044140:Receptor, Angiotensin, Type 1; D000804:Angiotensin II; C012877:angiotensin II, des-Asp(1)-des-Arg(2)-Ile(5)-; D000626:Aminopeptidases; D018826:CD13 Antigens