Rapid Biomolecular Trifluoromethylation Using Cationic Aromatic Sulfonate Esters as Visible-Light-Triggered Radical Photocages.
Rapid Biomolecular Trifluoromethylation Using Cationic Aromatic Sulfonate Esters as Visible-Light-Triggered Radical Photocages.
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DOI：
10.1021/jacs.3c08098
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发表时间：
2023-10
影响因子：
15
通讯作者：
Nicholas J Kuehl;Michael T. Taylor
中科院分区：
文献类型：
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作者：
Nicholas J Kuehl;Michael T. Taylor
本文描述了一种用于生物分子的自由基三氟甲基化的光降解方法。这是通过设计喹啉磺酸酯来实现的，所述喹啉磺酸酯在吸收可见光时通过磺酸酯的光解实现脱老化，以最终释放被生物分子中的π-亲核试剂捕获的游离三氟甲基自由基。这种光脱笼过程使蛋白质和蛋白质相互作用映射实验使用三氟甲基自由基，只需要1秒的反应时间和低光笼浓度。在这些实验中，以环境依赖性方式标记芳香族侧链，观察到对色氨酸（Trp）的选择性，然后是组氨酸（His）和酪氨酸（Tyr）。还证明了通过光去老化的可扩展的肽三氟甲基化，其中可以以5-7分钟的反应时间和良好的产率合成在色氨酸残基处具有三氟甲基基团的定制肽。
Described here is a photodecaging approach to radical trifluoromethylation of biomolecules. This was accomplished by designing a quinolinium sulfonate ester that, upon absorption of visible light, achieves decaging via photolysis of the sulfonate ester to ultimately liberate free trifluoromethyl radicals that are trapped by π-nucleophiles in biomolecules. This photodecaging process enables protein and protein-interaction mapping experiments using trifluoromethyl radicals that require only 1 s reaction times and low photocage concentrations. In these experiments, aromatic side chains are labeled in an environmentally dependent fashion, with selectivity observed for tryptophan (Trp), followed by histidine (His) and tyrosine (Tyr). Scalable peptide trifluoromethylation through photodecaging is also demonstrated, where bespoke peptides harboring trifluoromethyl groups at tryptophan residues can be synthesized with 5-7 min reaction times and good yields.