Oxytocin analogs with oxygen-containing side chains in position 3.
We have synthesized three oxytocin analogs containing an oxygen atom in the amino acid side chain in position 3 to determine the influences of increased side chain length and of hydrophilicity on the potencies and specificities of the resulting analogs. These three analogs: [3-O-methylhomoserine] oxytocin, [3-O-ethylserine] oxytocin, and [3-O-methylthreonine] oxytocin - have the following activities in U/mg: 490, 208, 265, milk ejection; 125, 129, 63, uterus in vivo; 0.2, 16, 0.03, antidiuretic; and 0.1, 0.5, 0.1, pressor. The results show that a longer side chain, [3-O-methylhomoserine] and [3-O-ethylserine] vs. [3-O-methylthreonine], tends to increase all activities. Moving the hydrophilic oxygen farther away from the peptide backbone, on the other hand, decreases vasopressin-like activities but increases or has no effect on oxytocin-like activities.
D000818:Animals; D004231:Diuresis / Q000187:drug effects; D005260:Female; D066298:In Vitro Techniques; D007202:Indicators and Reagents; D008893:Milk Ejection / Q000187:drug effects; D010121:Oxytocin / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology; D010643:Phenoxybenzamine / Q000494:pharmacology; D011247:Pregnancy; D051381:Rats; D013329:Structure-Activity Relationship; D014590:Uterine Contraction / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects
D007202:Indicators and Reagents; D010643:Phenoxybenzamine; D010121:Oxytocin