Center for Evolutionary Chemical Biology, Department of Chemistry, University of Copenhagen, Universitetsparken 5, 2100, Copenhagen, Denmark.
Angew Chem Int Ed Engl. 2018 Jul 2;57(27):8022-8026. doi: 10.1002/anie.201712589. Epub 2018 Apr 14.
Fluorobenzene probes for protein profiling through selective cysteine labeling have been developed by rational reactivity tuning. Tuning was achieved by selecting an electron-withdrawing para substituent in combination with variation of the number of fluorine substituents. Optimized probes chemoselectively arylated cysteine residues in proteins under aqueous conditions. Probes linked to azide, biotin, or a fluorophore were applicable to labeling of eGFP and albumin. Selective inhibition of cysteine proteases was also demonstrated with the probes. Additionally, probes were tuned for site-selective labeling of cysteine residues and for activity-based protein profiling in cell lysates.
通过合理的反应性调谐，开发了用于通过选择性半胱氨酸标记进行蛋白质谱分析的氟苯探针。通过选择吸电子的对位取代基并改变氟取代基的数量来实现调谐。优化后的探针在水相条件下选择性地芳基化蛋白质中的半胱氨酸残基。与叠氮化物、生物素或荧光团连接的探针可用于标记 eGFP 和白蛋白。还证明了这些探针可选择性抑制半胱氨酸蛋白酶。此外，还对探针进行了调谐，以实现半胱氨酸残基的位点选择性标记和细胞裂解物中的基于活性的蛋白质谱分析。
