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In‐Bead Screening of Hydroxamic Acids for the Identification of HDAC Inhibitors
Author(s) -
Qvortrup Katrine,
Nielsen Thomas E.
Publication year - 2016
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201511308
Subject(s) - bead , linker , hydroxamic acid , chemistry , combinatorial chemistry , photodissociation , chromatography , high throughput screening , polymer , stereochemistry , organic chemistry , biochemistry , materials science , computer science , composite material , operating system
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 IC 50 values in the nanomolar range.