Design and Synthesis of Minimalist Terminal Alkyne-Containing Diazirine Photo-Crosslinkers and Their Incorporation into Kinase Inhibitors for Cell- and Tissue-Based Proteome Profiling†
Dr. Zhengqiu Li
Department of Chemistry, National University of Singapore, 3 Science Drive 3, Singapore 117543 (Singapore) http://staff.science.nus.edu.sg/∼syao
Search for more papers by this authorPiliang Hao
School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551 (Singapore)
Search for more papers by this authorDr. Lin Li
Department of Chemistry, National University of Singapore, 3 Science Drive 3, Singapore 117543 (Singapore) http://staff.science.nus.edu.sg/∼syao
Search for more papers by this authorChelsea Y. J. Tan
Department of Chemistry, National University of Singapore, 3 Science Drive 3, Singapore 117543 (Singapore) http://staff.science.nus.edu.sg/∼syao
Search for more papers by this authorXiamin Cheng
Department of Chemistry, National University of Singapore, 3 Science Drive 3, Singapore 117543 (Singapore) http://staff.science.nus.edu.sg/∼syao
Search for more papers by this authorGrace Y. J. Chen
Department of Chemistry, National University of Singapore, 3 Science Drive 3, Singapore 117543 (Singapore) http://staff.science.nus.edu.sg/∼syao
Search for more papers by this authorProf. Dr. Siu Kwan Sze
School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551 (Singapore)
Search for more papers by this authorProf. Dr. Han-Ming Shen
Department of Physiology, National University of Singapore, 16 Medical Drive, Singapore 11794 (Singapore)
Search for more papers by this authorCorresponding Author
Prof. Dr. Shao Q. Yao
Department of Chemistry, National University of Singapore, 3 Science Drive 3, Singapore 117543 (Singapore) http://staff.science.nus.edu.sg/∼syao
Department of Chemistry, National University of Singapore, 3 Science Drive 3, Singapore 117543 (Singapore) http://staff.science.nus.edu.sg/∼syaoSearch for more papers by this authorDr. Zhengqiu Li
Department of Chemistry, National University of Singapore, 3 Science Drive 3, Singapore 117543 (Singapore) http://staff.science.nus.edu.sg/∼syao
Search for more papers by this authorPiliang Hao
School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551 (Singapore)
Search for more papers by this authorDr. Lin Li
Department of Chemistry, National University of Singapore, 3 Science Drive 3, Singapore 117543 (Singapore) http://staff.science.nus.edu.sg/∼syao
Search for more papers by this authorChelsea Y. J. Tan
Department of Chemistry, National University of Singapore, 3 Science Drive 3, Singapore 117543 (Singapore) http://staff.science.nus.edu.sg/∼syao
Search for more papers by this authorXiamin Cheng
Department of Chemistry, National University of Singapore, 3 Science Drive 3, Singapore 117543 (Singapore) http://staff.science.nus.edu.sg/∼syao
Search for more papers by this authorGrace Y. J. Chen
Department of Chemistry, National University of Singapore, 3 Science Drive 3, Singapore 117543 (Singapore) http://staff.science.nus.edu.sg/∼syao
Search for more papers by this authorProf. Dr. Siu Kwan Sze
School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551 (Singapore)
Search for more papers by this authorProf. Dr. Han-Ming Shen
Department of Physiology, National University of Singapore, 16 Medical Drive, Singapore 11794 (Singapore)
Search for more papers by this authorCorresponding Author
Prof. Dr. Shao Q. Yao
Department of Chemistry, National University of Singapore, 3 Science Drive 3, Singapore 117543 (Singapore) http://staff.science.nus.edu.sg/∼syao
Department of Chemistry, National University of Singapore, 3 Science Drive 3, Singapore 117543 (Singapore) http://staff.science.nus.edu.sg/∼syaoSearch for more papers by this authorFunding 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.
Graphical Abstract
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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