The synthesis and pharmacological properties of 4-decarboxamido-8-lysine-vasopressin, 5-decarboxamido-8-lysine-vasopressin, and their 1-deamino analogues.

Analogues of Wysine-vasopressin in which the carboxamide groups on the glutamine and asparagine residues at positions 4 and 5 are replaced individually by hydrogen have been synthesized by the p-nitrophenyl ester method of peptide synthesis and tested for some of the pharmacological activities characteristic of this pressor-antidiuretic hormone of the posterior pituitary gland. The 4-decarboxamido-8lysine-vasopressin ([4-oc-aminobutyric acid]-S-lysine-vasopressin) has an antidiuretic potency of approximately 700 units per mg, nearly 3 times the potency of S-lysine-vasopressin. It also possesses approximately 25% of the avian vasodepressor activity, 20 % of the oxytocic activity, and 4 % of the pressor activity of 8-lysine-vasopressin, whereas 5decarboxamido-8-lysine-vasopressin ([S-alanine]+lysinevasopressin) does not exhibit an appreciable degree of any of these activities. Thus the carboxamide group of the asparagine residue at position 5 of 8-lysine-vasopressin appears to play an important role in determining the pharmacological effects of the hormone. The corresponding ldeamino analogues of the 4and 5-decarboxamido-8-lysinevasopressins, in which the free amino group on the half-cystine residue at position 1 is replaced by hydrogen, have also been synthesized. 1-Deamino-4-decarboxamido8-lysine-vasopressin possesses extremely high antidiuretic activity (730 units per mg), low pressor activity (3.5 units per mg), and the same oxytocic and avian vasodepressor activities as 4-decarboxamido+lysine-vasopressin, whereas l-deamino-5-decarboxamido-8-lysine-vasopressin is practically inactive. The successive replacement of the carboxamide and amino groups on the glutamine and half-cystine residues