Biological activities of some new arginine vasopressin analogues containing unusual amino acids.

Solid-phase synthesis methods were applied to prepare some arginine vasopressin (AVP) analogues containing L- or D-pipecolic acids or alpha-L-homoproline in position 7, D-Cys in position 6, D-Val in position 4, O-alkylated D- or L-Tyr in position 2 and Pmp [1-(beta-mercapto-beta, beta-cyclopentamethylidenepropionic acid)] in position 1. Antidiuretic, vasopressor, antidiuretic antagonist and vasopressor antagonist activities were measured by biological methods. Antidiuretic effects were observed for all analogues. Pip7-AVPPmp1D-Tyr(Et)2D-Val4AVP and Mpa1dGly-NH-CH3(9) AVP had higher antidiuretic activities than that of AVP. None of the analogues exhibited an antidiuretic antagonist effect. With the exception of Pip7-AVP, none of the analogues had a vasopressor effect. Small vasopressor antagonist effects were found for DPip7AVP and Mpa1, DPip7AVP. The pharmacological significance of these new AVP analogues and the relationship between the chemical structure and biological activity are discussed.