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

Victor J. Hruby, K. K. Deb, Diane M. Yamamoto, Mac E. Hadley, W. Y. Chan

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

[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.

Original languageEnglish (US)
Pages (from-to)7-12
Number of pages6
JournalJournal of Medicinal Chemistry
Volume22
Issue number1
DOIs
StatePublished - Feb 1 1979

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

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