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Design and Synthesis of Minimalist Terminal Alkyne-Containing Diazirine Photo-Crosslinkers and Their Incorporation into Kinase Inhibitors for Cell- and Tissue-Based Proteome Profiling

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  • Funding was provided by the National Medical Research Council (NMRC/1260/2010) to H.-M.S. and S.Q.Y. and the Ministry of Education (MOE2012-T2-1-116). We thank Dr. Andrew Emili (Toronto) for helpful discussions of MS results.

Abstract

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Less is more: A minimalist “clickable” photo-crosslinker (see scheme) was incorporated with numerous small-molecule kinase inhibitors. The resulting probes were used for both in vitro (cell lysates) and in situ (live cells) proteome profiling, for large-scale identification of their potential cellular kinase targets and shows improved outcomes over previous probes.

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