HATs off: Selective synthetic inhibitors of the histone acetyltransferases p300 and PCAF

Ontario D. Lau, Tapas K. Kundu, Raymond E. Soccio, Slimane Ait-Si-Ali, Ehab M. Khalil, Alex Vassilev, Alan P. Wolffe, Yoshihiro Nakatani, Robert G. Roeder, Philip A. Cole

Research output: Contribution to journalArticlepeer-review

Abstract

Histone acetyltransferases (HATs) play important roles in the regulation of gene expression. In this report, we describe the design, synthesis, and application of peptide CoA conjugates as selective HAT inhibitors for the transcriptional coactivators p300 and PCAF. Two inhibitors (Lys-CoA for p300 and H3-CoA-20 for PCAF) were found to be potent (IC50 almost equal to 0.5 μM) and selective (~200-fold) in blocking p300 and PCAF HAT activities. These inhibitors were used to probe enzymatic and transcriptional features of HAT function in several assay systems. These compounds should be broadly useful as biological tools for evaluating the roles of HATs in transcriptional studies and may serve as lead agents for the development of novel antineoplastic therapeutics.

Original languageEnglish (US)
Pages (from-to)589-595
Number of pages7
JournalMolecular cell
Volume5
Issue number3
DOIs
StatePublished - 2000
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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