Discovery, synthesis and biochemical profiling of purine-2, 6-dione derivatives as inhibitors of the human poly(A)-selective ribonuclease Caf1. Issue 19 (1st October 2015)

• Record Type: Journal Article
• Authors: Jadhav, Gopal P.; Kaur, Ishwinder; Maryati, Maryati; Airhihen, Blessing; Fischer, Peter M.; Winkler, G. Sebastiaan
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 25:Issue 19(2015)
• Page Start: 4219
• Page End: 4224
• Publication Date: 2015-10-01
• Subjects: AQSLVVAGRVWNNM-UHFFFAOYSA-N -- BXVIXXCUEAJVED-UHFFFAOYSA-N -- ALBGHTKLFNLZMH-UHFFFAOYSA-N -- KAGAFRMBDGELJJ-UHFFFAOYSA-N -- SKJRMDARIDUDJO-UHFFFAOYSA-N -- KRVTWBWNBUGKOM-UHFFFAOYSA-N -- IUUFKCMEKHRZTO-UHFFFAOYSA-N -- UGXPPMHVOXYAKN-UHFFFAOYSA-N -- GCUIPJVTHMMXQC-UHFFFAOYSA-N -- GMMRACBVDJXXRU-UHFFFAOYSA-N -- MZPIGKQZSXYQQK-UHFFFAOYSA-N -- ZWLOFVLXNOZKNG-UHFFFAOYSA-N -- AVBQYYJZMJKIAP-UHFFFAOYSA-N -- QJZWLILWASSSHU-UHFFFAOYSA-N -- WCSKFJQTKVFPMJ-UHFFFAOYSA-N -- MAYFSZKATLHDLG-UHFFFAOYSA-N -- YVVYEMSBMRNOTE-UHFFFAOYSA-N -- ZUWQRQPOYBDHOI-UHFFFAOYSA-N -- LGXVVAZFZIWFJR-UHFFFAOYSA-N -- ITTTVNWVCMFMMP-UHFFFAOYSA-N -- XDMUHKKYUNALHW-UHFFFAOYSA-N -- XDUTVTQACWYOMX-UHFFFAOYSA-N -- UYIBJVHFPVYPRA-UHFFFAOYSA-N -- UPCWECPFBVRPRB-UHFFFAOYSA-N -- BTKSXPOKBAHJCN-UHFFFAOYSA-N; Ribonuclease -- Deadenylase -- Caf1/CNOT7 -- PARN -- Mg2+ dependent nuclease; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2015.07.095
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: 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.