Biofunctional evaluation of two hydrogen bonds stabilizing the beta-turn in the acyclic component of oxytocin.

The depsipeptide [8-alpha-hydroxyisocaproic acid, 9-glycolic amide]-oxytocin, which has ester linkages replacing the peptide linkages between the 7th and 8th and the 8th and 9th residues of oxytocin, has been synthesized by a (6 + 3) condensation of Boc-tocinoic acid with Pro-O-HyIc-O-Glyc-NH2, followed by deprotection of the resulting product. The analog exhibited the following activities in rats: 258 +/- 11 and 28 +/- 5 U/mg, uterus in vitro in the absence and presence, respectively, of Mg+2; 54 +/- 4 U/mg, uterus in vivo; 19.3 +/- 2.1 U/mg, milk ejection; 0.153 +/- 0.026 U/mg, antidiuretic activity; and no pressor activity. The need for the presence of the peptide linkages mentioned above as sources for internal hydrogen bonds to stabilize the "biologically significant" conformation is discussed.