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Many attempts have been performed to improve the performance of isoTOP-ABPP, mainly focused on cysteine reactive electrophile probes, cleavable biotin-azide tags, and heavy isotope incorporations ( Various probes recently introduced (summarized in Figure 5C) include (i) IA-alkyne based probes such as chloropyridine (RB2) and fluoronitrobenzene (ERW3) (Shannon et al., 2014), a photocaged bromomethyl ketone (CBK) ( N -propargylmaleimide, NPM) ( Different cleavable biotin-azide tags: protease-cleavable biotin-azide tags for CuAAC-mediated conjugation (TEV protease), chemically cleavable azobenzene (Azo) linkers (Qian and Weerapana, 2017) (Figure 7), and photocleavable biotin-azide tags such as reductive dimethyl labeling (termed rdTOP-ABPP for triplex quantification) (Yang et al., 2018) and multiplexed thiol reactivity profiling (MTRP) (Tian et al., 2017), maleimide-activated (Figure 8)

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