Evaluating
the efficiency and selectivity of photoaffinity-labeling
of recombinant proteins by the small-molecule probes. (a) Evaluating
the BTK labeling efficiency using in-gel fluorescence (top panels).
For reaction setup, 0.5 μg of BTK (final concentration ≈0.1
μM), 0.2 μM small-molecule probe, 10 μM Dasatinib
(for competition only) in 50 μL of PBS were used. For photoirradiation,
a hand-held UV lamp with a wavelength of 302 nm for ACT (5 min) and
BP (20 min) or 365 nm for DA (10 min) was used. (b) Evaluating the
BRD4 labeling efficiency using in-gel fluorescence (top panels). For
reaction setup, 0.4 μg of BRD4 (final concentration ≈0.4
μM), 0.2 μM small-molecule probe, 5 μg of BSA, and
10 μM JQ-1 (for competition only) in 50 μL of PBS were
used. The equal loading of proteins was verified by SYPRO Ruby staining
of the same gels (bottom panels). See Supporting Information for procedures of click chemistry with TAMRA-azide
and polyacrylamide gel electrophoresis.