Solution conformations of the peptide backbone for DPDPE and its β‐MePhe4‐substituted analogs

G. V. NIKIFOROVICH, O. M. PRAKASH, CATHERINE A. GEHRIG, VICTOR J. HRUBY

Research output: Contribution to journalArticle

31 Scopus citations

Abstract

The solution structures of DPDPE, a conformationally restricted pentapeptide with the sequence H‐Tyr1‐d‐Pen2‐Gly3‐Phe4‐d‐Pen5‐OH, and its four β‐MePhe4‐substituted analogs were examined by a combined approach including the NMR measurements in DMSO and water as well as independent energy calculations. It was concluded that several low energy conformers of DPDPE backbone satisfy the NMR data obtained in this study as well as in previous studies by other authors. These possible solution conformers of DPDPE in both DMSO and water share virtually the same type of cyclic backbone structure, with the Gly3 residue in a conformation close to a γ‐turn, and the Phe4 residue in a conformation close to α‐helical torsion angles. They differ in the space arrangements of the flexible Tyr1 moiety. The solution structures of the β‐MePhe4‐substituted analogs of DPDPE are interesting. For analogs with an S‐configuration at the Cα atom in the Phe4 residue, the cyclic backbone conformations resemble those of DPDPE itself, whereas for analogs with an R‐configuration at the Cα atom, the backbone conformation is somewhat different. This observation is in line with the high biological potencies and selectivities displayed by the former compounds but not by the latter ones. It was noted also that as far as the peptide backbone conformers are concerned, some of the possible DPDPE conformers in water are similar to the previously suggested model for the δ‐receptor‐bound conformation of DPDPE, becoming virtually identical to this conformation by rotating the side chains of the Tyr1 and the Phe4 residues.

Original languageEnglish (US)
Pages (from-to)347-361
Number of pages15
JournalInternational journal of peptide and protein research
Volume41
Issue number4
DOIs
StatePublished - Apr 1993

Keywords

  • DPDPE conformation
  • backbone conformation
  • calculations
  • conformation
  • energy
  • energy calculations for DPDPE

ASJC Scopus subject areas

  • Biochemistry

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