Development of a fluorogenic probe with a transesterification switch for detection of histone deacetylase activity

Reisuke Baba, Yuichiro Hori, Shin Mizukami, Kazuya Kikuchi

Research output: Contribution to journalArticlepeer-review

60 Citations (Scopus)

Abstract

Histone deacetylases (HDACs) are key enzymatic regulators of many cellular processes such as gene expression, cell cycle, and tumorigenesis. These enzymes are attractive targets for drug development. However, very few simple methods for monitoring HDAC activity have been reported. Here, we have developed a fluorogenic probe, K4(Ac)-CCB, which consists of the histone H3 peptide containing acetyl-Lys and a coumarin fluorophore with a carbonate ester. By the simple addition of the probe to a HDAC solution, enzyme activity was clearly detected through spontaneous intramolecular transesterification, which renders the probe fluorescent. In addition, K4(Ac)-CCB can be applied to the evaluation of HDAC inhibitor activity. This is the first report to demonstrate the monitoring of HDAC activity by using a one-step procedure. Thus, our novel fluorogenic probe will provide a powerful tool for epigenetic research and the discovery of HDAC-targeted drugs.

Original languageEnglish
Pages (from-to)14310-14313
Number of pages4
JournalJournal of the American Chemical Society
Volume134
Issue number35
DOIs
Publication statusPublished - 2012 Sep 5
Externally publishedYes

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

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