在亮啡肽中通过 1,4-二取代[1,2,3]三唑对酰胺的系统取代及其对 δ 阿片受体活性的影响。
Systematic replacement of amides by 1,4-disubstituted[1,2,3]triazoles in Leu-enkephalin and the impact on the delta opioid receptor activity.
机构信息
Laboratoire de chimie supramoléculaire, département de chimie, Université de Sherbrooke, Nord Sherbrooke, QC, Canada.
出版信息
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.
摘要
使用 Cu(I)-催化的叠氮-炔环加成反应，在混合经典有机相和固相肽合成方法中，我们合成了亮氨酸脑啡肽的四个类似物，以系统地将酰胺替换为 1,4-二取代[1,2,3]三唑。所得的肽模拟物通过竞争性结合、收缩试验和 ERK1/2 磷酸化进行了表征。本研究表明，在 Phe 和 Leu 之间带有三唑的类似物保留了一些效力，超过了其他所有类似物，这表明亮氨酸脑啡肽最后一个酰胺的氢键接受能力对于肽的生物活性是必不可少的。
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