Proton NMR and CD solution conformation determination and opioid receptor binding studies of a dynorphin A(1-17) model peptide

Joseph B. Vaughn, John W. Taylor

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

The opioid peptide dynorphin A(1-17) contains a peptide segment in residues 7-15 with the potential to form an amphiphilic β-strand. This amphiphilic structure may, like the amphiphilic α-helices found in many other peptide hormones, be an important determinant of its interactions with membranes and receptors. In order to investigate and characterize these interactions, we have synthesized a 17-residue dynorphin analogue (YGGFLKKVKPKVKVKSS) that incorporates a peptide model of this amphiphilic secondary structure with minimized homology (25%) relative to the native sequence. This peptide exhibits the full biological potency of dynorphin in assays of κ-opioid receptor binding, and is more selective for this type of opioid receptor than the natural peptide. The conformation of the model peptide in aqueous solution has been investigated in detail by NMR spectroscopy. The values of the NHCHa coupling constants together with rotating frame NOEs indicate the presence of an amphiphilic structure together with some β-strand structure in residues 7-15, and demonstrate that a peptide model that stabilizes this structure in aqueous solution and enhances κ-opioid receptor selectivity can be successfully designed using alternating lysine and valine residues.

Original languageEnglish (US)
Pages (from-to)135-146
Number of pages12
JournalBiochimica et Biophysica Acta (BBA)/Protein Structure and Molecular
Volume999
Issue number2
DOIs
StatePublished - Nov 30 1989
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology

Keywords

  • Amphiphilic structure
  • Dynorphin
  • Model peptide
  • NMR, two dimensional
  • β-Strand

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