Collect. Czech. Chem. Commun. 1984, 49, 137-140

The effect of some structural changes in the molecule of vasopressin on the duration of antidiuretic action

Tomislav Bartha, Pavel Hrbasa, Jana Škopkováa, Hans Vilhardtb, Martin Flegelc and Karel Jošta

a Institute of Organic Chemistry and Biochemistry, Czechoslovak Academy of Sciences, 166 10 Prague 6, ČSSR
b Department of Medical Physiology C, University Copenhagen, Panum Institute, Copenhagen N, Denmark
c Léčiva, 140 00 Prague - Modřany, ČSSR


The effect of two structural variations in the molecule of [8-D-arginine]deamino-vasopressin on the prolongation of the antidiuretic action of the analogues in non-anesthetised rats was studied. The replacement of glutamine in position 4 of the peptide chain with a suitable amino acid has prolonged the half-life of the antidiuretic effect. A more prolonged antidiuretic effect was obtained when the stabilization of the cyclic structure of [8-D-arginine]deamino vasopressin was performed by replacement of the disulfidic bridge by the monocarba bridge. The binding and activating constants (adenylate cyclase) in a membrane fraction of the rat kidney were compared with the factors influencing the metabolic stability of the molecule of the individual analogues.