title: Potent V2 vasopressin antagonists with structural changes at their C-terminals.
abstract: 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.
authors: Department of Pharmacology, College of Physicians and Surgeons of Columbia University, New York, NY 10032.
authors: W H
authors: WH
authors: Sawyer
authors: K
authors: K
authors: Bankowski
authors: A
authors: A
authors: Misicka
authors: E
authors: E
authors: Nawrocka
authors: M
authors: M
authors: Kruszynski
authors: S
authors: S
authors: Stoev
authors: W A
authors: WA
authors: Klis
authors: J P
authors: JP
authors: Przybylski
authors: M
authors: M
authors: Manning
mesh_terms: D000818:Animals; D001127:Arginine Vasopressin / Q000037:antagonists & inhibitors* / Q000138:chemical synthesis; D001681:Biological Assay; D005260:Female; D051381:Rats; D013329:Structure-Activity Relationship
chemical_list: D001127:Arginine Vasopressin