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

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

  • Bioorg Med Chem Lett. 2015 Oct 1;25(19):4219-24. doi: 10.1016/j.bmcl.2015.07.095.
Gopal P Jadhav 1,  Ishwinder Kaur 1,  Maryati Maryati 1,  Blessing Airhihen 2,  Peter M Fischer 3,  G Sebastiaan Winkler 4
Affiliations

Affiliations

  • 1 School of Pharmacy, Centre for Biomolecular Sciences, University of Nottingham, University Park, Nottingham NG7 2RD, UK.
  • 2 School of Pharmacy, Centre for Biomolecular Sciences, University of Nottingham, University Park, Nottingham NG7 2RD, UK; School of Pharmacy, University of Nottingham, East Drive, University Park, Nottingham NG7 2RD, UK.
  • 3 School of Pharmacy, Centre for Biomolecular Sciences, University of Nottingham, University Park, Nottingham NG7 2RD, UK. Electronic address: [email protected].
  • 4 School of Pharmacy, Centre for Biomolecular Sciences, University of Nottingham, University Park, Nottingham NG7 2RD, UK; School of Pharmacy, University of Nottingham, East Drive, University Park, Nottingham NG7 2RD, UK. Electronic address: [email protected].
PMID: 26299350 DOI: 10.1016/j.bmcl.2015.07.095
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 Mg(2+) 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.

Keywords

Caf1/CNOT7; Deadenylase; Mg(2+) dependent nuclease; PARN; Ribonuclease.

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