title: In-Bead Screening of Hydroxamic Acids for the Identification of HDAC Inhibitors.
abstract: 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.
authors.affiliation: Department of Chemistry, Technical University of Denmark, Kgs. Lyngby, 2800, Denmark.
authors.forename: Katrine
authors.initials: K
authors.lastname: Qvortrup
authors.affiliation: Department of Chemistry, Technical University of Denmark, Kgs. Lyngby, 2800, Denmark. ten@sund.ku.dk.|Singapore Centre on Environmental Life Sciences Engineering, Nanyang Technological University, 637551, Singapore, Singapore. ten@sund.ku.dk.
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Nielsen
mesh_terms: D056572:Histone Deacetylase Inhibitors / Q000032:analysis*; D006877:Hydroxamic Acids / Q000737:chemistry*; D008856:Microscopy, Fluorescence
chemical_list: D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids
keywords: HDAC inhibitors; combinatorial libraries; in-bead screening; photolabile linker