Synthesis and some pharmacological properties of three new analogues of arginine-vasopressin modified in positions 1,2,4 and 9.
We have synthesized three new analogues of arginine-vasopressin (AVP) to determine some of the structural features that account for antagonistic potency. These analogues are as follows: 4-glutamic acid (gamma-N,N-diethylamide)-8-arginine-vasopressin (I), N,N-diethylamide 1-(1-mercaptocyclohexaneacetic acid)-2-0-methyltyrosine- 4-glutamic acid (gamma-N,N-diethylamide)-8-arginine-vasopressin (II) and 1-(1-mercaptocyclohexaneacetic acid)-2-0-methyltyrosine-4-glutamic acid (gamma-glycine amide)-8-arginine-vasopressin (III). Analogues II and III are weak and moderate antagonists of the vasopressor response to AVP, respectively. Analogue III only exhibits a weak anti-antidiuretic activity. Analogue I lacks antagonistic effects in both systems.
Lammek
B
B
Institute of Chemistry, University of Gdańsk, Poland.
Derdowska
I
I
Melin
P
P
D000595:Amino Acid Sequence; D000818:Animals; D001127:Arginine Vasopressin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D055598:Chemical Phenomena; D002621:Chemistry; D005260:Female; D008969:Molecular Sequence Data; D051381:Rats; D011919:Rats, Inbred Strains
C061760:argipressin, (1-mercapto-cyclohexaneacetic acid)(1)-O-methyl-Tyr(2)-glutamic acid (gamma-Gly-amide)(4)-; D001127:Arginine Vasopressin; C061758:argipressin, glutamic acid (gamma-N,N-diethylamide)(4)-; C061759:vasopressin, N,N-diethylamide 1-(1-mercaptocyclohexaneacetic acid)-2-O-methyl-Tyr-4-glutamic acid (gamma-N,N-diethylamide)-8-Arg-