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

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

卷:23

Article

Proteau-Gagne, Arnaud¹  Rochon, Kristina²  Roy, Melissa²  Albert, Pierre-Julien²  Guerin, Brigitte^3,4  Gendron, Louis^2,4  Dory, Yves L.^1,4 

[1] Univ Sherbrooke, Dept Chim, Lab Chim Supramol, Nord Sherbrooke, PQ J1H 5N4, Canada

[2] Univ Sherbrooke, Dept Physiol & Biophys, Nord Sherbrooke, PQ J1H 5N4, Canada

[3] Univ Sherbrooke, Dept Med Nucl & Radiobiol, Nord Sherbrooke, PQ J1H 5N4, Canada

[4] Univ Sherbrooke, Inst Pharmacol Sherbrooke, Nord Sherbrooke, PQ J1H 5N4, Canada

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

DOI  :  10.1016/j.bmcl.2013.08.020

来源: Elsevier

【 摘 要 】

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. (C) 2013 Elsevier Ltd. All rights reserved.

【 授权许可】

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