Identification of novel bromodomain inhibitors of Trypanosoma cruzi bromodomain factor 2 (TcBDF2) using a fluorescence polarization-based high-throughput assay

Vista sencilla de ítem
dc.citation.titleAntimicrobial Agents and Chemotherapy
dc.citation.volume68
dc.contributor.orcidhttp://orcid.org/0000-0001-5986-7459
dc.creatorTavernelli, Luis Emilio
dc.creatorAlonso, Victoria Lucía
dc.creatorPeña, Imanol
dc.creatorRodríguez Araya, Elvio
dc.creatorManarin, Romina
dc.creatorCantizani, Juan
dc.creatorMartin, Julio
dc.creatorSalamanca, Juan
dc.creatorBamborough, Paul
dc.creatorCalderón, Felix
dc.creatorGabarro, Raquel
dc.creatorSerra, Esteban Carlos
dc.date.accessioned2025-02-28T15:29:55Z
dc.date.available2025-02-28T15:29:55Z
dc.date.issued2024-06-19
dc.description.abstractBromodomains are structural folds present in all eukaryotic cells that bind to other proteins recognizing acetylated lysines. Most proteins with bromodomains are part of nuclear complexes that interact with acetylated histone residues and regulate DNA replication, transcription, and repair through chromatin structure remodeling. Bromodomain inhibitors are small molecules that bind to the hydrophobic pocket of bromodomains, interfering with the interaction with acetylated histones. Using a fluorescent probe, we have developed an assay to select inhibitors of the bromodomain factor 2 of Trypanosoma cruzi (TcBDF2) using fluorescence polarization. Initially, a library of 28,251 compounds was screened in an endpoint assay. The top 350-ranked compounds were further analyzed in a dose-response assay. From this analysis, seven compounds were obtained that had not been previously characterized as bromodomain inhibitors. Although these compounds did not exhibit significant trypanocidal activity, all showed bona fide interaction with TcBDF2 with dissociation constants between 1 and 3 µM validating these assays to search for bromodomain inhibitors.
dc.description.filFil: Tavernelli, Luis Emilio. Instituto de Biología Molecular y Celular de Rosario (IBR-CONICET); Argentina.
dc.description.filFil: Tavernelli, Luis Emilio. GlaxoSmithKline Global Health; Spain.
dc.description.filFil: Alonso, Victoria Lucía. Instituto de Biología Molecular y Celular de Rosario (IBR-CONICET); Argentina.
dc.description.filFil: Alonso, Victoria Lucía. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas; Argentina.
dc.description.filFil: Peña, Imanol. GlaxoSmithKline Global Health; Spain.
dc.description.filFil: Rodríguez Araya, Elvio. Instituto de Biología Molecular y Celular de Rosario (IBR-CONICET); Argentina.
dc.description.filFil: Rodríguez Araya, Elvio. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas; Argentina.
dc.description.filFil: Manarin, Romina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas; Argentina.
dc.description.filFil: Cantizani, Juan. GlaxoSmithKline Global Health; Spain.
dc.description.filFil: Martin, Julio. GlaxoSmithKline Global Health; Spain.
dc.description.filFil: Salamanca, Juan. GlaxoSmithKline Global Health; Spain.
dc.description.filFil: Bamborough, Paul. GlaxoSmithKline. Molecular Design; United Kingdom.
dc.description.filFil: Calderón, Felix. GlaxoSmithKline Global Health; Spain.
dc.description.filFil: Gabarro, Raquel. GlaxoSmithKline Global Health; Spain.
dc.description.filFil: Serra, Esteban Carlos. Instituto de Biología Molecular y Celular de Rosario (IBR-CONICET); Argentina.
dc.description.filFil: Serra, Esteban Carlos. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas; Argentina.
dc.description.sponsorshipTres Cantos Open Lab Foundation: Tc261
dc.description.sponsorshipAgencia Nacional de Ciencia y Tecnología: PICT-2017-1978, PICT-2020-SERIEA-01704, PICT 2019-0526
dc.description.sponsorshipUniversidad Nacional de Rosario (UNR): 1BIO490
dc.format.extent1-12
dc.identifier.issn0066-4804
dc.identifier.urihttps://hdl.handle.net/2133/28980
dc.language.isoen
dc.publisherAmerican Society for Microbiology
dc.relation.publisherversionhttps://journals.asm.org/doi/epdf/10.1128/aac.00243-24
dc.relation.publisherversionhttps://doi.org/10.1128/aac.00243-24
dc.rightsopenAccess
dc.rights.holderTavernelli, Luis Emilio
dc.rights.holderAlonso, Victoria Lucía
dc.rights.holderPeña, Imanol
dc.rights.holderRodríguez Araya, Elvio
dc.rights.holderManarin, Romina
dc.rights.holderCantizani, Juan
dc.rights.holderMartin, Julio
dc.rights.holderSalamanca, Juan
dc.rights.holderBamborough, Paul
dc.rights.holderCalderón, Felix
dc.rights.holderGabarro, Raquel
dc.rights.holderSerra, Esteban Carlos
dc.rights.textAttribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectTrypanosoma
dc.subjectBromodomain
dc.subjectInhibitors
dc.titleIdentification of novel bromodomain inhibitors of Trypanosoma cruzi bromodomain factor 2 (TcBDF2) using a fluorescence polarization-based high-throughput assay
dc.typearticulo
dc.type.versionpublishedVersion

Archivos

Bloque original
Mostrando 1 - 1 de 1
Miniatura
Nombre:
Identification of novel bromodomain inhibitors of Trypanosoma cruzi bromodomain factor 2.pdf
Tamaño:
629.08 KB
Formato:
Adobe Portable Document Format
Descargar
Bloque de licencias
Mostrando 1 - 1 de 1
Nombre:
license.txt
Tamaño:
3.87 KB
Formato:
Item-specific license agreed upon to submission
Descripción:
Descargar

Colecciones

(FBIOyF) Departamento de Microbiología - Artículos