Premium
Rational Tuning of Fluorobenzene Probes for Cysteine‐Selective Protein Modification
Author(s) -
Embaby Ahmed M.,
Schoffelen Sanne,
Kofoed Christian,
Meldal Morten,
Diness Frederik
Publication year - 2018
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201712589
Subject(s) - chemistry , cysteine , fluorophore , fluorobenzene , substituent , biotin , proteases , combinatorial chemistry , azide , fluorescence , stereochemistry , biochemistry , enzyme , organic chemistry , physics , quantum mechanics , benzene
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.