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.