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

5 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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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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