Diacylglycerol lipases (DAGL) produce the endocannabinoid 2-arachidonoylglycerol, a key modulator of neurotransmitter release. Chemical tools that visualize endogenous DAGL activity are desired. Here, we report the design, synthesis and application of a triazole urea probe for DAGL equipped with a norbornene as a biorthogonal handle. The activity and selectivity of the probe was assessed with activity-based protein profiling. This probe was potent against endogenous DAGLα (IC₅₀ = 5 nM) and it was successfully applied as a two-step activity-based probe for labeling of DAGLα using an inverse electron-demand Diels–Alder ligation in living cells.

中文翻译：

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基于两步活动的二酰基甘油脂肪酶蛋白质分析†

二酰基甘油脂肪酶（DAGL）产生内源性大麻素2-花生四烯酰基甘油，这是神经递质释放的关键调节剂。需要可视化内源DAGL活性的化学工具。在这里，我们报道了装备有降冰片烯作为生物正交手柄的DAGL的三唑脲探针的设计，合成和应用。探针的活性和选择性通过基于活性的蛋白质谱进行评估。该探针对内源性DAGLα具有强效作用（IC ₅₀ = 5 nM），并已成功应用于活细胞中基于反电子需求的Diels-Alder连接的两步法基于活性的探针标记DAGLα。