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

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 com...

Descripción completa

Detalles Bibliográficos
Autores principales: Jadhav, Gopal P., Kaur, Ishwinder, Maryati, Maryati, Airhihen, Blessing, Fischer, Peter M., Winkler, G. Sebastiaan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier Science Ltd 2015
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4577731/
https://www.ncbi.nlm.nih.gov/pubmed/26299350
http://dx.doi.org/10.1016/j.bmcl.2015.07.095
_version_ 1782391002082836480
author Jadhav, Gopal P.
Kaur, Ishwinder
Maryati, Maryati
Airhihen, Blessing
Fischer, Peter M.
Winkler, G. Sebastiaan
author_facet Jadhav, Gopal P.
Kaur, Ishwinder
Maryati, Maryati
Airhihen, Blessing
Fischer, Peter M.
Winkler, G. Sebastiaan
author_sort Jadhav, Gopal P.
collection PubMed
description 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.
format Online
Article
Text
id pubmed-4577731
institution National Center for Biotechnology Information
language English
publishDate 2015
publisher Elsevier Science Ltd
record_format MEDLINE/PubMed
spelling pubmed-45777312015-10-26 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 Bioorg Med Chem Lett Article 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. Elsevier Science Ltd 2015-10-01 /pmc/articles/PMC4577731/ /pubmed/26299350 http://dx.doi.org/10.1016/j.bmcl.2015.07.095 Text en © 2015 The Authors http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Jadhav, Gopal P.
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
title Discovery, synthesis and biochemical profiling of purine-2,6-dione derivatives as inhibitors of the human poly(A)-selective ribonuclease Caf1
title_full Discovery, synthesis and biochemical profiling of purine-2,6-dione derivatives as inhibitors of the human poly(A)-selective ribonuclease Caf1
title_fullStr Discovery, synthesis and biochemical profiling of purine-2,6-dione derivatives as inhibitors of the human poly(A)-selective ribonuclease Caf1
title_full_unstemmed Discovery, synthesis and biochemical profiling of purine-2,6-dione derivatives as inhibitors of the human poly(A)-selective ribonuclease Caf1
title_short Discovery, synthesis and biochemical profiling of purine-2,6-dione derivatives as inhibitors of the human poly(A)-selective ribonuclease Caf1
title_sort discovery, synthesis and biochemical profiling of purine-2,6-dione derivatives as inhibitors of the human poly(a)-selective ribonuclease caf1
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4577731/
https://www.ncbi.nlm.nih.gov/pubmed/26299350
http://dx.doi.org/10.1016/j.bmcl.2015.07.095
work_keys_str_mv AT jadhavgopalp discoverysynthesisandbiochemicalprofilingofpurine26dionederivativesasinhibitorsofthehumanpolyaselectiveribonucleasecaf1
AT kaurishwinder discoverysynthesisandbiochemicalprofilingofpurine26dionederivativesasinhibitorsofthehumanpolyaselectiveribonucleasecaf1
AT maryatimaryati discoverysynthesisandbiochemicalprofilingofpurine26dionederivativesasinhibitorsofthehumanpolyaselectiveribonucleasecaf1
AT airhihenblessing discoverysynthesisandbiochemicalprofilingofpurine26dionederivativesasinhibitorsofthehumanpolyaselectiveribonucleasecaf1
AT fischerpeterm discoverysynthesisandbiochemicalprofilingofpurine26dionederivativesasinhibitorsofthehumanpolyaselectiveribonucleasecaf1
AT winklergsebastiaan discoverysynthesisandbiochemicalprofilingofpurine26dionederivativesasinhibitorsofthehumanpolyaselectiveribonucleasecaf1

Ejemplares similares