Proposed Conformations of Oxytocin and Selected Analogs in Dimethyl Sulfoxide as Deduced from Proton Magnetic Resonance Studies

A. I.Richard Brewster, V. J. Hruby, J. A. Glasel, A. E. Tonelli

Research output: Contribution to journalArticle

47 Scopus citations

Abstract

The 220-MHz nmr spectra have been obtained and assigned for oxytocin, deamino-oxytocin, [4-glycine]oxytocin, [2-valine]oxytocin, [7-D-proline]oxytocin, and [1-β-mercaptopropionic acid, 7-D-proline]oxytocin. Several deuterated derivatives were used for making unambiguous assignments. Conformational calculations based on measured values of the vicinal amide to α-proton coupling were used for proposing conformations for the molecules in dimethyl sulfoxide solution. Three energetically favorable conformations of oxytocin are found, one of which has a single intramolecular hydrogen bond involving the asparagine-5 backbone NH and the glutamine-4 carboxamide carbonyl. The tripeptide side chain is proposed to possess a trans-cis' junction to the ring and is folded toward the ring. In dimethyl sulfoxide oxytocin appears to possess a nonrigid conformation. Deamino-oxytocin possess a conformation similar to oxytocin. The proposed conformation for [4-glycine]oxytocin has two transannular bonds: the asparagine-5 peptide NH and carbonyl to the tyrosine-2 carbonyl and peptide NH, respectively. The conformation of [2-valine]oxytocin appears to be quite different from that of any of the other peptide analogs examined, with no intramolecular hydrogen bond. Both D-proline-7 analogs differ from oxytocin and deamino-oxytocin in the orientation of the tripeptide side chain with respect to the ring. The influence of the amino acid substitutions on the conformation is discussed.

Original languageEnglish (US)
Pages (from-to)5294-5304
Number of pages11
JournalBiochemistry
Volume12
Issue number26
DOIs
StatePublished - Dec 1 1973

ASJC Scopus subject areas

  • Biochemistry

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