Systematic replacement of amides by 1,4-disubstituted[1,2,3]triazoles in Leu-enkephalin and the impact on the delta opioid receptor activity

Bioorg Med Chem Lett. 2013 Oct 1;23(19):5267-9. doi: 10.1016/j.bmcl.2013.08.020. Epub 2013 Aug 12.

Abstract

Using Cu(I)-catalyzed azide-alkyne cycloaddition in a mixed classical organic phase and solid phase peptide synthesis approach, we synthesized four analogs of Leu-enkephalin to systematically replace amides by 1,4-disubstituted[1,2,3]triazoles. The peptidomimetics obtained were characterized by competitive binding, contractility assays and ERK1/2 phosphorylation. The present study reveals that the analog bearing a triazole between Phe and Leu retains some potency, more than all the others, suggesting that the hydrogen bond acceptor capacity of the last amide of Leu-enkephalin is essential for the biological activity of the peptide.

Keywords: 1,2,3 Triazole; Click chemistry; Delta opioid receptor; Leu-enkephalin; Peptidomimetics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amides / chemistry*
  • Binding, Competitive
  • Enkephalin, Leucine / chemistry*
  • Enkephalin, Leucine / pharmacology
  • Hydrogen Bonding
  • Inhibitory Concentration 50
  • Molecular Structure
  • Peptidomimetics
  • Receptors, Opioid, delta / chemistry*
  • Receptors, Opioid, delta / drug effects
  • Triazoles / chemistry*

Substances

  • Amides
  • Peptidomimetics
  • Receptors, Opioid, delta
  • Triazoles
  • Enkephalin, Leucine