Margot Acosta

Probing the molecular basis of antidiuretic specificity and duration of action with synthetic peptides

The individual structural alterations of AVP which bring about enhancement of A/V specificity are: (a) deamination of position one [3] ; (b) enhancement of lipophilicity at position 4 [ 1,8] and (c) substitution of Dfor L-arginine at position 8 [ 51. When all three changes were incorporated into one molecule the resulting peptide [ 1 deamino-4valine] 8-D-arginine vasopressin (dVDAVP) was found to be the most highly specific antidiuretic peptide ever reported [lo] . dVDAVP has undetectable vasopressor activity, antidiuretic activity about four times that of AVP and an A/V ratio of over 123 000 compared to 0.9 for AVP. It also exhibits a markedly prolonged duration of action similar to that previously observed for [ 1 -deamino] -8-D7arginine vasopressin (DDAVP) [7] . The present communiation summarizes our subsequent separately reported findings on the relative effects of these structural changes in contributing to (1) enhanced antidiuretic specificity [ 1 I] and (2)