Here, we report the chemical synthesis of two DPDPE analogues 7a (NOVA1) and 7b (NOVA2). This entailed the solid-phase synthesis of two enkephalin precursor chains followed by a Cu^I-catalyzed azide-alkyne cycloaddition, with the aim of improving in vivo analgesic efficacy versus DPDPE. NOVA2 showed good affinity and selectivity for the μ-opioid receptor (K_I of 59.2 nM, EC₅₀ of 12.9 nM, E_Max of 87.3%), and long lasting anti-nociceptive effects in mice when compared to DPDPE.

中文翻译：

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树脂点击化学介导的新型脑啡肽类似物具有强的抗伤害感受活性

在这里，我们报告了两个DPDPE类似物7a（NOVA1）和7b（NOVA2）的化学合成。这需要两条脑啡肽前体链的固相合成，然后是Cu ^I催化的叠氮化物-炔烃环加成反应，目的是与DPDPE相比提高体内止痛效果。与DPDPE相比，NOVA2对μ阿片样物质受体表现出良好的亲和力和选择性（K _I为59.2 nM，EC ₅₀为12.9 nM，E _Max为87.3％），并且在小鼠中具有持久的抗伤害感受作用。