BIOLOGICALLY-ACTIVE ANALOGS OF ARGININE-VASOPRESSIN CONTAINING CONFORMATIONALLY RESTRICTED DIPEPTIDE FRAGMENTS

In this study we described the synthesis and pharmacological propertie s of five new analogues of arginine vasopressin (AVP). Four of these a nalogues contained ethylene-bridged dipeptide Phe-Phe in positions 2 a nd 3; one had two N-Me-Phe residues. All new peptides were tested for vasopressor and antidiuretic activities. We also estimated the uteroto nic activities of these compounds in vitro. Three analogues were highl y potent V-1-antagonists. One of them, namely [Cpa(1),(Phe-Phe)(2,3),V al(4)]AVP, which seemed to not interact with either V-2 and oxytocic r eceptors, was outstandingly selective. It is interesting that the high antipressor potency of our second peptide, [(N-Me-Phe)(2,3)]AVP, was achieved without modification of position 1. Our results open new poss ibilities for the design of very potent and selective V-1-antagonists of AVP. (C) Munksgaard 1998.