Arginine vasopressin and its analogues--the influence of position 2 modification with 3,3-diphenylalanine enantiomers. Highly potent V2 agonists.

Eleven new analogues of arginine vasopressin (AVP) modified in position 2 by 3,3-diphenyl-L-alanine or its D-enantiomer (Dip or D-Dip) were synthesized and pharmacologically evaluated for their pressor, antidiuretic and in vitro uterotonic activities. Both the Dip and D-Dip modifications at position 2 of AVP are sufficient to completely change the pharmacological profile of the peptides. They preserve or increase antidiuretic activity, cause its prolongation, transform uterotonic property in antagonistic one and cancel the effect on blood pressure. Four of the new peptides ([Mpa1,D-Dip2]AVP, [Mpa1,D-Dip2,Val4]AVP, [Mpa1,D-Dip2,D-Arg8]VP, [Mpa1,D-Dip2,Val4,D-Arg8]VP) are exceptionally potent antidiuretic agents with significantly prolonged activities.