ArticleMethods in molecular biology (Clifton, N.J.)2025
Building Blocks for the Screening of Histone Deacetylase Inhibitors Using μSPOT.
Article in Methods in molecular biology (Clifton, N.J.), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Histone deacetylase (HDAC) inhibitors are approved as cancer chemotherapy and studied for the treatment of various diseases. However, there is a lack of isozyme-selective compounds to determine the biological role of each of the 11 HDACs, and to develop drugs applicable to a wider range of disorders. Here, we describe the synthesis of hydroxamic acid and trifluoromethyl ketone-containing building blocks and their use to synthesize libraries of HDAC-binding peptides. Modified peptides are synthesized via the SPOT method on cellulose discs that allow deprotection and solubilization to obtain printable DMSO stocks, which afford hundreds of library copies on assay-ready slides. Thus, multiple screening rounds can be performed on a single library. This method facilitates the screening of peptides as potential HDAC inhibitors with diverse selectivity and has already provided compounds active in cells.
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