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

作者：Jadhav Gopal P; Kaur Ishwinder; Maryati Maryati; Airhihen Blessing; Fischer Peter M^*; Winkler G Sebastiaan

来源：Bioorganic & Medicinal Chemistry Letters, 2015, 25(19): 4219-4224.

DOI：10.1016/j.bmcl.2015.07.095

• Ribonuclease
• Deadenylase
• Caf1/CNOT7
• PARN
• Mg2+ dependent nuclease

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.

• 出版日期2015-10-1