Rational Tuning of Fluorobenzene Probes for Cysteine‐Selective Protein Modification

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. Auf Cystein abstimmen: Die Reaktivität von chemischen Sonden für die selektive Arylierung am Cystein‐Schwefel in Proteinen wurde in zweidimensionaler Weise feinjustiert: über die Zahl der Fluorsubstituenten (siehe Schema) und über die Art eines zusätzlichen Substituenten. Die optimierten Sonden waren für die Proteinmarkierung, die selektive Hemmung von Cysteinproteasen und das aktivitätsbasierte Proteinprofilierung von Zelllysaten geeignet.