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

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• 作者：Arnaud Proteau-Gagn¨¦ ; Kristina Rochon ; M¨¦lissa Roy ; Pierre-Julien Albert ; Brigitte Gu¨¦rin ; Louis Gendron ; Yves L. Dory
• 关键词：Click chemistry ; Delta opioid receptor ; 1 ; 2 ; 3 Triazole ; Leu-enkephalin ; Peptidomimetics
• 刊名：Bioorganic and Medicinal Chemistry Letters
• 出版年：2013
• 出版时间：1 October, 2013
• 年：2013
• 卷：23
• 期：19
• 页码：5267-5269
• 全文大小：705 K

文摘

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.