[5-(N4,N4-Dimethylasparagine),8-lysine]vasopressin: the first 5-position neurohypophyseal hormone analogue to retain to retain significant antidiuretic potency.
In the proposed biologically active conformation of vasopressin at the antidiuretic receptor, the side-chain carboxamide group of the 5-position asparaginyl residue has been previously suggested to be the key active element in the hormone for its initiation of the antidiuretic response. [5-(N4,N4-Dimethylasparagine),8-lysine]vasopressin, the analogue in which the hydrogen atoms of the -NH2 portion of the primary carboxamide have been replaced by methyl groups, has been synthesized and found to retain about 3% of the antidiuretic potency of lysine-vasopressin (i.e., 5.5 +/- 0.3 units/mg). This result suggests that the hydrogen atoms of the carboxamide moiety are not essential for antidiuretic activity. In addition, the analogue possesses rat pressor, avian vasodepressor, and rat uterotonic potencies of 2.55 +/- 0.05, 0.39 +/- 0.03, and less than 0.05 units/mg, respectively.
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002645:Chickens; D004231:Diuresis / Q000187:drug effects; D005260:Female; D066298:In Vitro Techniques; D008236:Lypressin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D008297:Male; D008968:Molecular Conformation; D051381:Rats; D013329:Structure-Activity Relationship; D014590:Uterine Contraction / Q000187:drug effects
D008236:Lypressin; C023824:vasopressin, (5-(N(4),N(4)-dimethyl-Asn)-8-Lys)-