Synthesis of 7200 Small Molecules Based on a Substructural Analysis of the Histone Deacetylase Inhibitors Trichostatin and Trapoxin
- 30 November 2001
- journal article
- letter
- Published by American Chemical Society (ACS) in Organic Letters
- Vol. 3 (26) , 4239-4242
- https://doi.org/10.1021/ol016915f
Abstract
Seventy-two hundred potential inhibitors of the histone deacetylase (HDAC) enzyme family, based on a 1,3-dioxane diversity structure, were synthesized on polystyrene macrobeads. The compounds were arrayed for biological assays in a “one bead-one stock solution” format. Metal-chelating functional groups were used to direct the 1,3-dioxanes to HDAC enzymes, which are zinc hydrolases. Representative structures from this library were tested for inhibitory activity and the 1,3-dioxane structure was shown to be compatible with HDAC inhibition.Keywords
This publication has 9 references indexed in Scilit:
- The Sequence of the Human GenomeScience, 2001
- Guide to the draft human genomeNature, 2001
- Split−Pool Synthesis of 1,3-Dioxanes Leading to Arrayed Stock Solutions of Single Compounds Sufficient for Multiple Phenotypic and Protein-Binding AssaysJournal of the American Chemical Society, 2001
- Acetylation: a regulatory modification to rival phosphorylation?The EMBO Journal, 2000
- Structures of a histone deacetylase homologue bound to the TSA and SAHA inhibitorsNature, 1999
- Printing Small Molecules as Microarrays and Detecting Protein−Ligand Interactions en MasseJournal of the American Chemical Society, 1999
- Three proteins define a class of human histone deacetylases related to yeast Hda1pProceedings of the National Academy of Sciences, 1999
- Nuclear histone acetylases and deacetylases and transcriptional regulation: HATs off to HDACsCurrent Opinion in Chemical Biology, 1997
- A Mammalian Histone Deacetylase Related to the Yeast Transcriptional Regulator Rpd3pScience, 1996