[1-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: Research - peer-reviewArticle

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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 pAg 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.

LanguageEnglish (US)
Pages7-12
Number of pages6
JournalJournal of Medicinal Chemistry
Volume22
Issue number1
StatePublished - 1979

Fingerprint

Penicillamine
Peptide Hormones
Oxytocin
Leucine
Pharmacology
Assays
Hormones
Peptides
Oxytocics
Synthetic Chemistry Techniques
Solid-Phase Synthesis Techniques
Uterus
Gel Chromatography
Chromatography
Milk
Magnetic Resonance Spectroscopy
sephadex
Spin-lattice relaxation
Relaxation time
Gels

ASJC Scopus subject areas

  • Organic Chemistry

Cite this

[1-Penicillamine,2-leucine]oxytocin. Synthesis and pharmacological and conformational studies of a potent peptide hormone inhibitor. / Hruby, Victor J.; Deb, K. K.; Yamamoto, Diane M.; Hadley, Mac E.; Chan, W. Y.

In: Journal of Medicinal Chemistry, Vol. 22, No. 1, 1979, p. 7-12.

Research output: Research - peer-reviewArticle

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AU - Deb,K. K.

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AU - Hadley,Mac E.

AU - Chan,W. Y.

PY - 1979

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N2 - [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 pAg 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.

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