Synthesis and biological activities of arginine-vasopressin analogues with 4-hydroxyproline in position 7.
Three arginine-vasopressin (AVP) analogues in which the proline residue in position 7 was substituted with 4-hydroxyproline were synthesized by solid-phase techniques, and their biological activities were evaluated by antidiuretic, pressor, and uterotonic bioassays. The [7-trans-4-hydroxy-L-proline]AVP, the 1-desamino[7-trans-4-hydroxy-L-proline]AVP, and the 1-desamino[7-cis-4-hydroxy-L-proline]AVP analogues showed a high antidiuretic and strikingly high uterine activity, a sharp decrease in pressor activity, and a better antidiuretic and uterine to pressor selectivity than the parent compound, arginine-vasopressin. The uterine activities are the highest so far assayed in AVP analogues with replacements in position 7.
D000818:Animals; D001127:Arginine Vasopressin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D004231:Diuresis / Q000187:drug effects; D005260:Female; D006909:Hydroxyproline; D008968:Molecular Conformation; D011311:Pressoreceptors / Q000187:drug effects; D051381:Rats; D013329:Structure-Activity Relationship; D014599:Uterus / Q000187:drug effects
D001127:Arginine Vasopressin; D006909:Hydroxyproline