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

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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

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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

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

Bioorganic and Medicinal Chemistry Letters, Vol.25(19), pp.4219-4224

10/01/2015

DOI: https://doi.org/10.1016/j.bmcl.2015.07.095

PMID: 26299350

Abstract

Biochemistry

Molecular Medicine

Molecular Biology

Pharmaceutical Science

Drug Discovery

Clinical Biochemistry

Organic Chemistry

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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Title: Discovery, synthesis and biochemical profiling of purine-2,6-dione derivatives as inhibitors of the human poly(A)-selective ribonuclease Caf1
Creators: Gopal P. Jadhav (Author) - University of Nottingham
Ishwinder Kaur (Author) - University of Nottingham
Maryati Maryati (Author) - University of Nottingham;Muhammadiyah University of Surakarta
Blessing Airhihen (Author) - University of Nottingham
Peter M. Fischer (Author) - University of Nottingham
G. Sebastiaan Winkler (Author) - University of Nottingham
Publication Details: Bioorganic and Medicinal Chemistry Letters, Vol.25(19), pp.4219-4224
Series: 25
Number of pages: 6
Grant note: 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).
Identifiers: 991005929581402656
Academic Unit: Creighton University
Language: English
Resource Type: Journal article