Wang Shuo, He Xu, Li Junchen, Shi Enxue
State Key Laboratory of NBC Protection for Civilian, Beijing 102205, China.
Molecules. 2023 Dec 14;28(24):8083. doi: 10.3390/molecules28248083.
The multifunctional linker molecules are crucial for the bio-orthogonal reaction for proteomic target profiling. Herein, we wish to present a novel type of biotin-based tetra-functional bio-orthogonal linkers named BPPA which, possessing a unique photolabile phenacyl ester motif, were readily prepared in 85-90% yields by a simple and green one-step protocol from commercially available and inexpensive reagents of biotin acids and 4'-ethynyl/azido 2-bromoacetophenones. The typical click reaction of BPPA linkers and via copper-catalyzed azide-alkyne cycloaddition (CuAAC) took place easily, resulting in the corresponding BPPA-triazole adducts and in nearly quantitative yields. A further cleavability evaluation of and demonstrated that the expected C-O bond detachment could be accomplished efficiently and rapidly by UV irradiation or by ammonia hydrolysis, respectively, resulting in the residual (hydroxyl)acetylphenyl triazole fragment supposed to be attached to proteins during biological manipulations. The BPPA linkers, with dual clickable options of either the terminal azide or alkyne clickable group, exhibit high potentials for various CuAAC-oriented bio-orthogonal reactions.
多功能连接分子对于蛋白质组靶标分析的生物正交反应至关重要。在此，我们希望介绍一种新型的基于生物素的四功能生物正交连接体，名为BPPA，它具有独特的光不稳定苯甲酰酯基序，通过简单且绿色的一步法，以85 - 90%的产率，由市售且廉价的生物素酸试剂和4'-乙炔基/叠氮基2-溴苯乙酮轻松制备而成。BPPA连接体通过铜催化的叠氮-炔环加成反应（CuAAC）与典型的点击反应能够轻松发生，生成相应的BPPA-三唑加合物，产率接近定量。对[此处原文可能缺失相关物质指代]的进一步可切割性评估表明，预期的C-O键断裂分别可以通过紫外线照射或氨水解高效且快速地完成，从而在生物操作过程中产生预期会连接到蛋白质上的残留（羟基）乙酰苯基三唑片段。BPPA连接体具有末端叠氮或炔基可点击基团的双重可点击选择，在各种面向CuAAC的生物正交反应中展现出高潜力。
