title: Systematic replacement of amides by 1,4-disubstituted[1,2,3]triazoles in Leu-enkephalin and the impact on the delta opioid receptor activity.
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.
authors.affiliation: Laboratoire de chimie supramoléculaire, département de chimie, Université de Sherbrooke, Nord Sherbrooke, QC, Canada.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Proteau-Gagné
authors.forename: Kristina
authors.initials: K
authors.lastname: Rochon
authors.forename: Mélissa
authors.initials: M
authors.lastname: Roy
authors.forename: Pierre-Julien
authors.initials: PJ
authors.lastname: Albert
authors.forename: Brigitte
authors.initials: B
authors.lastname: Guérin
authors.forename: Louis
authors.initials: L
authors.lastname: Gendron
authors.forename: Yves L
authors.initials: YL
authors.lastname: Dory
mesh_terms: D000577:Amides / Q000737:chemistry*; D001667:Binding, Competitive; D004743:Enkephalin, Leucine / Q000737:chemistry* / Q000494:pharmacology; D006860:Hydrogen Bonding; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D057786:Peptidomimetics; D017465:Receptors, Opioid, delta / Q000737:chemistry* / Q000187:drug effects; D014230:Triazoles / Q000737:chemistry*
chemical_list: D000577:Amides; D057786:Peptidomimetics; D017465:Receptors, Opioid, delta; D014230:Triazoles; D004743:Enkephalin, Leucine
keywords: 1,2,3 Triazole; Click chemistry; Delta opioid receptor; Leu-enkephalin; Peptidomimetics