Sydnone Reporters for Highly Fluorogenic Copper-Free Click Ligations
Sydnone Reporters for Highly Fluorogenic Copper-Free Click Ligations
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DOI：
10.1021/acs.joc.7b03004
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发表时间：
2018-02-16
影响因子：
3.6
通讯作者：
Friscourt, Frederic
中科院分区：
文献类型：
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作者：
Favre, Camille;de Cremoux, Lucie;Friscourt, Frederic
生物正交荧光开启反应对于生物共轭、化学反应性和材料组装等多种现象的灵敏实时检测具有吸引力。在此，我们描述了使用 3,4-二取代的苯乙烯酮（一类单一的介离子偶极子）与荧光二苯并环辛炔 Fl-DIBO 进行高荧光开启的无铜点击环加成反应。与时间相关的密度泛函理论计算相一致，吡唑环加合物具有高荧光性，具有引人注目的光物理性质，包括优异的荧光增强（高达 240 倍）、高量子产率（超过 45%）和大斯托克斯位移（超过 100 nm）。此外，4-氯代酮与 Fl-DIBO 的良好稳定性和反应性使我们能够将其用作化学报告分子，用于复杂细胞提取物中修饰蛋白的挑战性检测，在免洗条件下具有精致的特异性。这种新颖的荧光系统显着扩展了我们的化学生物学工具箱，并且应该在无数的应用中受益。
Bioorthogonal fluorescent turn-on reactions are attractive for the sensitive real-time detection of a variety of phenomena including bioconjugation, chemical reactivity, and material assembly. Herein we describe the use of 3,4-disubstituted sydnones, a singular class of mesoionic dipoles, for highly fluorescent turn-on copper-free click cycloadditions with the fluorogenic dibenzocyclooctyne Fl-DIBO. Coherent with time-dependent density functional theory calculations, the pyrazole cycloadducts were found to be highly fluorescent with compelling photophysical properties including excellent fluorescence enhancement (up to 240-fold), high quantum yields (over 45%), and large Stokes shift (over 100 nm). Furthermore, the good stability and reactivity of 4-chlorosydnones with Fl-DIBO allowed us to employ them as chemical reporters for the challenging detection of modified-proteins in complex cellular extracts, with exquisite specificity in no-wash conditions. This novel fluorogenic system significantly expands our chemical biology toolbox and should be beneficial in countless applications.