Synthesis and biological activity of angiotensin II analogues containing a Val-His replacement, Val psi[CH(CONH2)NH]His.
The dipeptide mimic Val psi[CH(CONH2)NH]His (4) was incorporated into angiotensin II (AII) analogues to provide an octapeptide saralasin derivative (29) as well as tetrapeptide analogue 19. Three C-terminal tetrapeptides (21, 25, and 28) were also prepared. All compounds were tested for their ability to displace 3H-AII from rabbit adrenal gland homogenate and as antagonists of AII and AI on guinea pig ileum. The octapeptide analogue 29 was 700 times less active than the parent peptide 30. All the C-terminal fragments 19, 21, 25, and 28 have no measurable AII antagonist activity. Of the four tetrapeptide fragments, only 21 showed any appreciable binding activity.
Mohan
R
R
Berlex Laboratories, Inc., Cedar Knolls, New Jersey 07927.
Chou
Y L
YL
Bihovsky
R
R
Lumma
W C
WC
Erhardt
P W
PW
Shaw
K J
KJ
D015059:1-Sarcosine-8-Isoleucine Angiotensin II / Q000031:analogs & derivatives*; D000311:Adrenal Glands / Q000378:metabolism; D000595:Amino Acid Sequence; D000803:Angiotensin I / Q000037:antagonists & inhibitors; D000804:Angiotensin II / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000378:metabolism; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D004151:Dipeptides; D006168:Guinea Pigs; D007082:Ileum / Q000502:physiology; D008969:Molecular Sequence Data; D009119:Muscle Contraction / Q000187:drug effects; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000494:pharmacology; D011817:Rabbits; D011945:Receptors, Angiotensin / Q000378:metabolism; D012504:Saralasin / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology
D057911:Angiotensin Receptor Antagonists; D004151:Dipeptides; D009842:Oligopeptides; D010446:Peptide Fragments; D011945:Receptors, Angiotensin; D000804:Angiotensin II; C070465:N-(2-amino-1-(aminocarbonyl)-3-methylbutyl)histidine; C070466:angiotensin II, Sar(1)-Val(5)-Ile(8)-; D000803:Angiotensin I; D015059:1-Sarcosine-8-Isoleucine Angiotensin II; D012504:Saralasin