4-Proline and 4-hydroxyproline analogs of arginine vasopressin: Role of the proline substitution in the two β-turns of vasopressin

[4-L-Proline]arginine vasopressin, [4-D-proline]arginine vasopressin, [4-hydroxyproline]arginine vasopressin and [4-proline, 7-hydroxyproline] arginine vasopressin were synthesized and found to have antidiuretic activities of 91±4, 1.7±0.2, 1.0±0.1 and 4.4±1.0 units/mg, respectively. None of these analogs exhibited a significant level of rat pressor activity. The observed activities of these and other analogs with substitutions at position 4 and/or 7 are discussed on the basis of hypotheses and data bearing on the solution conformation of vasopressins.