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

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

Research output: Contribution to journalArticle

4 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)4219-4224
Number of pages6
JournalBioorganic and Medicinal Chemistry Letters
Volume25
Issue number19
DOIs
StatePublished - Oct 1 2015
Externally publishedYes

Fingerprint

Poly A
Ribonucleases
Derivatives
Messenger RNA
RNA Cleavage
RNA Stability
Protein Biosynthesis
Catalytic Domain
Ions
RNA
Enzymes
purine
poly(A)-specific ribonuclease

All Science Journal Classification (ASJC) codes

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

Cite this

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

Jadhav, Gopal ; Kaur, Ishwinder ; Maryati, Maryati ; Airhihen, Blessing ; Fischer, Peter M. ; Winkler, G. Sebastiaan. / Discovery, synthesis and biochemical profiling of purine-2,6-dione derivatives as inhibitors of the human poly(A)-selective ribonuclease Caf1. In: Bioorganic and Medicinal Chemistry Letters. 2015 ; Vol. 25, No. 19. pp. 4219-4224.
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