TY - JOUR
T1 - Discovery, synthesis and biochemical profiling of purine-2,6-dione derivatives as inhibitors of the human poly(A)-selective ribonuclease Caf1
AU - Jadhav, Gopal P.
AU - Kaur, Ishwinder
AU - Maryati, Maryati
AU - Airhihen, Blessing
AU - Fischer, Peter M.
AU - Winkler, G. Sebastiaan
N1 - Publisher Copyright:
© 2015 The Authors. Published by Elsevier Ltd.
Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 2015/10/1
Y1 - 2015/10/1
N2 - 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.
AB - 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.
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U2 - 10.1016/j.bmcl.2015.07.095
DO - 10.1016/j.bmcl.2015.07.095
M3 - Article
C2 - 26299350
AN - SCOPUS:84945496059
VL - 25
SP - 4219
EP - 4224
JO - Bioorganic and Medicinal Chemistry Letters
JF - Bioorganic and Medicinal Chemistry Letters
SN - 0960-894X
IS - 19
ER -