Synthesis and Opioid Activity of Tyr1-ψ[(Z)CF=CH]-Gly2 and Tyr1-ψ[(S)/(R)-CF3CH-NH]-Gly2 Leu-enkephalin Fluorinated Peptidomimetics

Somnath Narayan Karad, Mohan Pal, Rachel S. Crowley, Thomas E. Prisinzano, Ryan A. Altman

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

Abstract

We describe the design, synthesis, and opioid activity of fluoroalkene (Tyr1-ψ[(Z)CF=CH]-Gly2) and trifluoroethylamine (Tyr1-ψ[(S)/(R)-CF3CH-NH]-Gly2) analogues of the endogenous opioid neuropeptide, Leu-enkephalin. The fluoroalkene peptidomimetic exhibited low nanomolar functional activity (5.0±2 nm and 60±15 nm for δ- and μ-opioid receptors, respectively) with a μ/δ-selectivity ratio that mimics that of the natural peptide. However, the trifluoroethylamine peptidomimetics, irrespective of stereochemistry, did not activate the opioid receptors, which suggest that bulky CF3 substituents are not tolerated at this position.

Original languageEnglish
Pages (from-to)571-576
Number of pages6
JournalChemMedChem
Volume12
Issue number8
DOIs
StatePublished - Apr 20 2017

Bibliographical note

Publisher Copyright:
© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Keywords

  • amide bonds
  • enkephalin
  • fluorine
  • opioids
  • peptidomimetics

ASJC Scopus subject areas

  • Drug Discovery
  • General Pharmacology, Toxicology and Pharmaceutics
  • Molecular Medicine
  • Biochemistry
  • Pharmacology
  • Organic Chemistry

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