Biofunctional evaluation of a hydrogen bond stabilizing the beta -turn in the acyclic part of oxytocin.

In a continued effort to determine the importance of the hydrogen bonds for stabilization of the biologically active conformation of oxytocin, deamino-[9-glycolicamide] oxytocin was synthesized in order to study, in this respect, the hydrogen bond between the peptide N-H of Gly9 and the C=O of Cys6. In this analog the amide linkage between residues at positions 8 and 9 is replaced by an ester. Thus, the residue at position 9 cannot be involved in hydrogen bond formation with the C=O of Cys6. Deamino-[9-glycolicamide] oxytocin exhibited 134 ± 13 U/mg and 355 ± 48 U/mg of uterotonic activity in absence and in presence, respectively, of Mg2+, 108 ± 8 U/mg of milk-ejecting activity, 0.35 ± 0.03 U/mg of pressor activity and 2.5 ± 0.1 U/mg of antidiuretic activity. It is concluded that the hydrogen bond under question is not critical for the conformation required for biofunctional interaction of oxytocin with its receptors in the uterus, mammary gland and other target organs.