Rational Tuning of Fluorobenzene Probes for Cysteine-Selective Protein Modification

被引：60

作者：

Embaby, Ahmed M. ^{[1
]}

Schoffelen, Sanne ^{[1
]}

Kofoed, Christian ^{[1
]}

Meldal, Morten ^{[1
]}

Diness, Frederik ^{[1
]}

机构：

[1] Univ Copenhagen, Dept Chem, Ctr Evolutionary Chem Biol, Univ Pk 5, DK-2100 Copenhagen, Denmark

来源：

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION | 2018年 / 57卷 / 27期

关键词：

arylation; enzymes; fluorination; inhibitors; protein modification; FREE N-ARYLATION; ACTIVE-SITE; UNACTIVATED FLUOROBENZENES; NITRILASE FAMILY; REACTIVITY; CHEMISTRY; ELECTROPHILES; INHIBITORS; DISCOVERY; ENZYMES;

D O I：

10.1002/anie.201712589

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

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.

引用

页码：8022 / 8026

页数：5

共 56 条

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