In-Bead Screening of Hydroxamic Acids for the Identification of HDAC Inhibitors
Dr. Katrine Qvortrup
Department of Chemistry, Technical University of Denmark, Kgs. Lyngby, 2800 Denmark
Search for more papers by this authorCorresponding Author
Prof. Dr. Thomas E. Nielsen
Department of Chemistry, Technical University of Denmark, Kgs. Lyngby, 2800 Denmark
Singapore Centre on Environmental Life Sciences Engineering, Nanyang Technological University, 637551 Singapore, Singapore
Search for more papers by this authorDr. Katrine Qvortrup
Department of Chemistry, Technical University of Denmark, Kgs. Lyngby, 2800 Denmark
Search for more papers by this authorCorresponding Author
Prof. Dr. Thomas E. Nielsen
Department of Chemistry, Technical University of Denmark, Kgs. Lyngby, 2800 Denmark
Singapore Centre on Environmental Life Sciences Engineering, Nanyang Technological University, 637551 Singapore, Singapore
Search for more papers by this authorAbstract
A one bead–one compound screening format is presented. Following solid-phase synthesis on a photolabile linker, library compounds were readily released and screened inside polymer beads. The release of screening compounds was readily controlled by varying photolysis time and light intensity. Dose-response experiments were carried out to effectively distinguish high- and low-affinity ligands. A library containing 55 800 compounds was synthesized and screened in a fluorometric assay, thereby identifying potent HDAC inhibitors with IC50 values in the nanomolar range.
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