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

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.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

Jadhav GP,Kaur I,Maryati M,Airhihen B,Fischer PM,Winkler GS

doi

10.1016/j.bmcl.2015.07.095

subject

Has Abstract

pub_date

2015-10-01 00:00:00

pages

4219-24

issue

19

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(15)00814-8

journal_volume

25

pub_type

杂志文章

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