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

Mol Cell. 2000 Mar;5(3):589-95. doi: 10.1016/s1097-2765(00)80452-9.


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 (IC(50) approximately = 0.5 microM) and selective (approximately 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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acetyltransferases / antagonists & inhibitors*
  • Acyl Coenzyme A / chemistry*
  • Acyl Coenzyme A / pharmacology
  • Antineoplastic Agents / chemistry
  • Histone Acetyltransferases
  • Histones / metabolism*
  • Lysine / chemistry*
  • Lysine / pharmacology
  • Nucleic Acid Synthesis Inhibitors / chemistry
  • Oligopeptides / chemistry*
  • Oligopeptides / pharmacology
  • Saccharomyces cerevisiae Proteins*


  • Acyl Coenzyme A
  • Antineoplastic Agents
  • Histones
  • Nucleic Acid Synthesis Inhibitors
  • Oligopeptides
  • Saccharomyces cerevisiae Proteins
  • Acetyltransferases
  • Histone Acetyltransferases
  • Lysine