Potent V2 vasopressin antagonists with structural changes at their C-terminals.
A variety of structural changes were made in the C-terminals of four potent antidiuretic (V2) antagonists. The parent analogs were all derivatives of [1-(beta-mercapto-beta,beta-cyclopentamethylenepropionic acid)]arginine-vasopressin, d(CH2)5AVP, namely d(CH2)5[D-Phe2,Ile4]AVP, d(CH2)5[D-Ile2,Ile4]AVP, d(CH2)5[D-Tyr(Et)2, Val4]AVP and d(CH2)5[D-Tyr(Et)2,Ile4]AVP. A number of amino acid amides were substituted for the C-terminal 9-glycinamide without reducing their V2-antagonistic potencies in rats. Many non-amino acid structures were also tolerated at the C-terminals of these antagonists and this end of these peptides can be prolonged without interfering with antagonistic potencies. Such altered V2-antagonists may be useful for the development of radioactive ligands, affinity labels and in affinity columns for studies on antidiuretic receptors. These C-terminal modifications also provide useful information for the further development of potent and specific V2-antagonists which can be valuable pharmacological tools and also promise to become useful clinically for the treatment of excessive water retention.
Sawyer
W H
WH
Department of Pharmacology, College of Physicians and Surgeons of Columbia University, New York, NY 10032.
Bankowski
K
K
Misicka
A
A
Nawrocka
E
E
Kruszynski
M
M
Stoev
S
S
Klis
W A
WA
Przybylski
J P
JP
Manning
M
M
D000818:Animals; D001127:Arginine Vasopressin / Q000037:antagonists & inhibitors* / Q000138:chemical synthesis; D001681:Biological Assay; D005260:Female; D051381:Rats; D013329:Structure-Activity Relationship
D001127:Arginine Vasopressin