[l-Penicillamine, 2-leucine]oxytocin. Synthesis and Pharmacological and Conformational Studies of a Potent Peptide Hormone Inhibitor

[1-Penicillamine, 2-leucine]oxytocin was synthesized by the solid-phase method of peptide synthesis and purified by partition chromatography on Sephadex G-25, followed by gel filtration. The peptide was found to be a very potent competitive inhibitor of oxytocin in the oxytocic assay with a pA₂ of 7.14 and an inhibitor of oxytocin in the milk-ejecting assay. The compound showed no agonist activity in either of these assays, and its inhibitory activity at the uterus was of prolonged duration. The ¹³C nuclear magnetic resonance spectral properties and the ¹³C T₁(spin-lattice) relaxation times of [Pen¹,Leu²]oxytocin were determined, and the results were compared with previous studies of [Pen¹] oxytocin, a related competitive inhibitor, and oxytocin, the native hormone agonist. These studies indicated that the hormone inhibitors [Pen¹,Leu²] oxytocin and [Pen¹]oxytocin have similar conformational and dynamic properties which are different than those of the agonist, oxytocin.