Discovery, synthesis and biochemical profiling of purine-2,6-dione derivatives as inhibitors of the human poly(A)-selective ribonuclease Caf1

Gopal P. Jadhav, Ishwinder Kaur, Maryati Maryati, Blessing Airhihen, Peter M. Fischer, G. Sebastiaan Winkler

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

Eukaryotic mRNA contains a 3′ poly(A) tail, which plays important roles in the regulation of mRNA stability and translation. Well-characterized enzymes involved in the shortening of the poly(A) tail include the multi-subunit Ccr4-Not deadenylase, which contains the Caf1 (Pop2) and Ccr4 catalytic components, and poly(A)-specific ribonuclease (PARN). Two Mg2+ ions present in the active sites of these ribonucleases are required for RNA cleavage. Here, we report the discovery, synthesis and biochemical profiling of purine-2,6-dione derivatives as (sub)micromolar inhibitors of Caf1.

Original languageEnglish (US)
Pages (from-to)4219-4224
Number of pages6
JournalBioorganic and Medicinal Chemistry Letters
Volume25
Issue number19
DOIs
StatePublished - Oct 1 2015
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

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