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

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

doi:10.1016/j.bmcl.2015.07.095

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

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

Research output: Contribution to journal › Article › peer-review

6 Scopus citations

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.

Original language	English (US)
Pages (from-to)	4219-4224
Number of pages	6
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	25
Issue number	19
DOIs	https://doi.org/10.1016/j.bmcl.2015.07.095
State	Published - Oct 1 2015
Externally published	Yes

All Science Journal Classification (ASJC) codes

Biochemistry
Molecular Medicine
Molecular Biology
Pharmaceutical Science
Drug Discovery
Clinical Biochemistry
Organic Chemistry

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10.1016/j.bmcl.2015.07.095

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

In: Bioorganic and Medicinal Chemistry Letters, Vol. 25, No. 19, 01.10.2015, p. 4219-4224.

Research output: Contribution to journal › Article › peer-review

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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.",

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AU - Airhihen, Blessing

AU - Fischer, Peter M.

AU - Winkler, G. Sebastiaan

N1 - Funding Information: This work was supported by the Medical Research Council (grant G1100205 ), the Islamic Development Bank (scholarship to MM), and the Schlumberger Foundation (Faculty for the Future award to BA). Publisher Copyright: © 2015 The Authors. Published by Elsevier Ltd.

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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

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