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

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

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.

• Journal Article Type: Article
• Acceptance Date: Jul 31, 2015
• Online Publication Date: Aug 6, 2015
• Publication Date: Oct 1, 2015
• Deposit Date: Sep 14, 2017
• Publicly Available Date: Nov 19, 2018
• Electronic ISSN: 1464-3405
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• Volume: 25
• Issue: 19
• Pages: 4219-4224
• DOI: https://doi.org/10.1016/j.bmcl.2015.07.095
• Public URL: https://nottingham-repository.worktribe.com/output/1113260
• Publisher URL: https://www.sciencedirect.com/science/article/pii/S0960894X15008148
• PMID: 26299350