Medicinal Chemistry & Chemical Biology, Short talk
MC-027

Kinase Templated Abiotic Reaction

J. Saarbach1, E. Lindberg1, S. Folliet1, S. Georgeon2, O. Hantschel2*, S. Soleimanpour1*
1Faculty of Science, Department of Organic Chemistry, NCCR Chemical Biology, University of Geneva, 30 quai Ernest Ansermet, Geneva, Switzerland, 2Swiss Institute for Experimental Cancer Research (ISREC), NCCR Chemical Biology, School of Life Sciences, École Polytechnique Fédérale de Lausanne (EPFL), CH-1015 Lausanne, Switzerland

Protein kinases are essential regulators of cellular signalling and have been at the centre stage of drug discovery for the past decade. The successful development of kinase inhibitors demonstrated that kinases were drugable and triggered tremendous research effort in this area. However, inhibitors developed so far often target the conserved ATP binding site of the protein and thus are lacking selectivity[1], and the more selective ones are targeting an inactive form of the protein. These features limit their use as chemical probes to sense kinase activity. Herein we report a strategy[2] based on two reacting probes[3] targeting both nucleotide and substrate binding sites. The reaction[4] used allows to use fluorescence readout to selectively sense Abl of Src kinase activity both in biochemical and fixed whole cell experiments.

[1] O. Hantschel, U. Rix, T. Buerckstuemmer, U. Schmidt, M. Kneidinger, K. L. Bennett, I. Kaupe, W. Ellmeier, P. Valent, G. Superti-Furga, Blood 2007, 110, 207b-207b.
[2] K. Gorska, I. Keklikoglou, U. Tschulena, N. Winssinger, Chem Sci 2011, 2, 1969-1975.
[3] K. K. Sadhu, T. Eierhoff, W. Römer, N. Winssinger, J Am Chem Soc 2012, 134, 20013-20016.
[4] D. Chang, E. Lindberg, N. Winssinger, J Am Chem Soc 2017, 139, 1444-1447.