Cyclic enkephalin analogs that are hybrids of DPDPE-related peptides and Met-enkephalin-Arg-Gly-Leu: Prohormone analogs that retain good potency and selectivity for δ opioid receptors

H. Bartosz-Bechowski, P. Davis, J. Slaninova, E. Malatynska, D. Stropova, F. Porreca, H. I. Yamamura, Victor J. Hruby

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

We report here on the binding affinity and bioassay results of cyclic enkephalin analogs comprising a cyclic moiety and C-terminal fragment of MERGL, where ME denotes methionine enkephalin. MERGL (YGGFMRGL) has been suggested to be cleaved enzymatically by membrane-bound enkephalinase 24.11 to leave ME and the tripeptide RGL. In our study we have synthesized hybrids of DPDPE or DPLCE and the C-terminal tripeptide RGL in order to mimic a prohormone able to cross the blood-brain barrier. The study has shown that of the homologs presented here, analogs of DPLCE often are more potent at delta opioid receptors both in binding affinity and in bioactivity at the MVD, than DPDPE. Our hypothesis that hybrids (consisting of the drug and the spacer for the carrier) could be designed which would either have no opioid activity or, alternatively, be by themselves very active, has been verified.

Original languageEnglish (US)
Pages (from-to)329-336
Number of pages8
JournalJournal of Peptide Research
Volume53
Issue number3
DOIs
StatePublished - May 3 1999

    Fingerprint

Keywords

  • DPDPE analogs
  • Enzymatically cleavable peptides
  • Opioid peptides
  • Prodrugs
  • Structure-activity relationships

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology

Cite this