Biofunctional evaluation of a hydrogen bond stabilizing the conformation in the cyclic part of oxytocin

[5-beta-Malamidic acid]oxytocin was synthesized to study the importance of the hydrogen bond between the C=O of Tyr2 and the peptide N-H of Asn5 for the stabilization of a biologically functional conformation of oxytocin. This analog lacks the peptide N-H at residue 5 required for the formation of a hydrogen bond with the C-O of Tyr2. [5-beta-Malamidic acid] oxytocin exhibited 45.1 +/- 2.5 U/mg and 65.6 +/- 5.9 U/mg of uterotonic activity, in vitro, in the absence and in the presence, respectively, of Mg2+, 147 +/- 14 U/mg of uterotonic activity in vivo, 203 +/- 13 U/mg of milk-ejecting activity, 0.37 +/- 0.03 U/mg of pressor activity and 0.32 +/- 0.29 U/mg of antidiuretic activity. It is concluded that devoid of the hydrogen bond under question, an oxytocin-like peptide can still assume the conformation needed to interact with the oxytocin receptors.