Synthesis and some pharmacological properties of deamino(4-threonine,8-D-arginine)vasopressin and deamino(8-D-arginine)vasopressin, highly potent and specific antidiuretic peptides, and (8-D-arginine)vasopressin and deamino-arginine-vasopressin.
Deamino[4-threonine,8-D-arginine]vasopressin (dTDAVP), deamino[8-D-arginine]vasopressin (dDAVP), [8-D-arginine[vasopressin (DAVP), and deamino-arginine-vasopressin (dAVP) were synthesized by the solid-phase method and tested for their biological activities. dTDAVP has an antidiuretic potency of 793+/-95 units/mg and undetectable vasporessor activity, less than 0.02unit/mg. The antidiuretic-pressor (A/P) ratio of dTDAVP is greater than 39 000. dDAVP has an antidiuretic potency of 1200+/-126 units/mg and a vasopressor potency of 0.39+/-0.02; its A/P ratio is thus 3000. DAVP has an antidiuretic potency of 253+/-44 units/mg, a vasopressor potency of 1.1+/-0.04 units/mg, and an A/P ratio of 240. The A/P ratios of dDAVP and DAVP are much higher than those originally reported. dAVP has an antidiuretic potency of 1745+/-385 units/mg, a vasopressor potency of 346+/-13, and an A/P ratio of 5; values are in general agreement with those in the literature. Threonine subsitution has thus brought about a significant enhancement in antidiuretic specificity, a finding entirely consistent with earlier observations that enhancement of lipophilicity at position 4 alone or in combination in arginine-vasopressin can lead to enhanced antidiuretic specificity.
D000818:Animals; D001127:Arginine Vasopressin / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D003894:Deamino Arginine Vasopressin / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000494:pharmacology; D004231:Diuresis / Q000187:drug effects; D005260:Female; D066298:In Vitro Techniques; D008274:Magnesium / Q000494:pharmacology; D008297:Male; D009130:Muscle, Smooth / Q000187:drug effects; D051381:Rats; D013329:Structure-Activity Relationship; D013912:Threonine / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000494:pharmacology; D014590:Uterine Contraction / Q000187:drug effects; D014667:Vasopressins / Q000031:analogs & derivatives*
D014667:Vasopressins; D001127:Arginine Vasopressin; D013912:Threonine; C012865:vasopressin, deamino(4-Thr-8-Arg)-; D003894:Deamino Arginine Vasopressin; D008274:Magnesium