The Synthesis and Pharmacological Properties of 4-Decarboxamido-8-lysine-vasopressin, 5-Decarboxamido-8-lysine-vasopressin, and Their 1-Deamino Analogues
Analogues of 8-lysine-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 ch...
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Published in | The Journal of biological chemistry Vol. 242; no. 20; pp. 4806 - 4812 |
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Main Authors | , |
Format | Journal Article |
Language | English |
Published |
United States
American Society for Biochemistry and Molecular Biology
25.10.1967
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Subjects | |
Online Access | Get full text |
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Summary: | Analogues of 8-lysine-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-8-lysine-vasopressin ([4-α-aminobutyric
acid]-8-lysine-vasopressin) has an antidiuretic potency of approximately 700 units per mg, nearly 3 times the potency of 8-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 5-decarboxamido-8-lysine-vasopressin ([5-alanine]-8-lysine-vasopressin) 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 1-deamino analogues of the 4- and 5-decarboxamido-8-lysine-vasopressins, 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-decarboxamido-8-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-8-lysine-vasopressin, whereas 1-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 at positions 4 and 1, respectively, of 8-lysine-vasopressin thus results in a striking enhancement of antidiuretic
activity coupled with a marked decrease in pressor activity. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0021-9258 1083-351X |
DOI: | 10.1016/S0021-9258(18)99528-1 |