The synthesis and some pharmacological properties of (2-L-DOPA)-oxytocin.
The first reported synthetic analogue of a naturally occurring peptide with a residue of L-3,4-dihydroxyphenylalanine (L-DOPA) was prepared by coupling N-carbobenzoxy-S-benzylcysteinyl-L-DOPA azide with isoleucylglutaminylasparaginyl-S-benzylcysteinylprolylleuclglycinamide. The protecting groups were removed from the resultant nonapeptide derivative by sodium in liquid ammonia and the peptide analogue was formed by short term oxidation of the dithiol-containing compound. It was isolated by sequential partition chromatography and exclusion chromatography on Sephadex G-25. It was unstable at neutral or alkaline pH. [2-L-DOPA]-oxytocin was found to possess a minimum milk-ejection-like activity of 54 +/- 9 U/mg and uterotonic activity of 26 +/- 4 U/mg. These potencies are approximately 12% and 5% of the corresponding potencies of oxytocin.
D000818:Animals; D001681:Biological Assay; D055598:Chemical Phenomena; D002621:Chemistry; D005260:Female; D007774:Lactation / Q000187:drug effects; D007980:Levodopa / Q000031:analogs & derivatives* / Q000494:pharmacology; D008321:Mammary Glands, Animal / Q000187:drug effects / Q000378:metabolism; D008892:Milk / Q000378:metabolism; D010121:Oxytocin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D011247:Pregnancy; D051381:Rats; D013056:Spectrophotometry, Ultraviolet; D013329:Structure-Activity Relationship; D014599:Uterus / Q000187:drug effects
D007980:Levodopa; D010121:Oxytocin