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dc.contributor.authorPierce, Raymond J.
dc.contributor.authorJung, Manfred
dc.contributor.authorLancelot, Julien
dc.contributor.authorAlmlof, Ingrid
dc.contributor.authorSchultz, Johan
dc.contributor.authorSippl, Wolfgang
dc.contributor.authorRomier, Christophe
dc.contributor.authorKaraman, Berin
dc.contributor.authorSchiedel, Matthias
dc.contributor.authorMarek, Martin
dc.date.accessioned2021-03-06T10:44:30Z
dc.date.available2021-03-06T10:44:30Z
dc.date.issued2015
dc.identifier.citationSchiedel M., Marek M., Lancelot J., Karaman B., Almlof I., Schultz J., Sippl W., Pierce R. J. , Romier C., Jung M., "Fluorescence-Based Screening Assays for the NAD(+)-Dependent Histone Deacetylase smSirt2 from Schistosoma mansoni", JOURNAL OF BIOMOLECULAR SCREENING, cilt.20, ss.112-121, 2015
dc.identifier.issn1087-0571
dc.identifier.othervv_1032021
dc.identifier.otherav_ebd7b70e-b12c-4fd8-99c6-f9aa8271c9f6
dc.identifier.urihttp://hdl.handle.net/20.500.12627/154864
dc.identifier.urihttps://doi.org/10.1177/1087057114555307
dc.description.abstractSirtuins are NAD(+)-dependent histone deacetylases (HDACs) that cleave off acetyl but also other acyl groups from the E-amino group of lysines in histones and other substrate proteins. Five sirtuin isoforms are encoded in the genome of the parasitic pathogen Schistosoma mansoni. During its life cycle, S. mansoni undergoes drastic changes in phenotype that are associated with epigenetic modifications. Previous work showed strong effects of hSirt2 inhibitors on both worm life span and reproduction. Thus, we postulate smSirt2 as a new antiparasite target. We report both the optimization of a homogeneous fluorescence-based assay and the development of a new heterogeneous fluorescence-based assay to determine smSirt2 activity. The homogeneous assay uses a coumarin-labeled acetyl lysine derivative, and the heterogeneous version is using a biotinylated and fluorescence-labeled oligopeptide. Magnetic streptavidin-coated beads allow higher substrate loading per well than streptavidin-coated microtiter plates and make it possible to screen for inhibitors of either smSirt2 or its human isoform (hSirt2) for selectivity studies. We also present hits from a pilot screen with inhibitors showing an IC50 lower than 50 mu M. Binding of the hits to their targets is rationalized by docking studies using a homology model of smSirt2.
dc.language.isoeng
dc.subjectKİMYA, ANALİTİK
dc.subjectKimya
dc.subjectTemel Bilimler (SCI)
dc.subjectBİYOKİMYA VE MOLEKÜLER BİYOLOJİ
dc.subjectMoleküler Biyoloji ve Genetik
dc.subjectTıp
dc.subjectSağlık Bilimleri
dc.subjectTemel Tıp Bilimleri
dc.subjectBiyokimya
dc.subjectYaşam Bilimleri
dc.subjectBiyoteknoloji
dc.subjectMoleküler Biyoloji ve Genetik
dc.subjectSitogenetik
dc.subjectAnalitik Kimya
dc.subjectTemel Bilimler
dc.subjectBİYOKİMYASAL ARAŞTIRMA YÖNTEMLERİ
dc.subjectYaşam Bilimleri (LIFE)
dc.subjectBİYOTEKNOLOJİ VE UYGULAMALI MİKROBİYOLOJİ
dc.subjectMikrobiyoloji
dc.subjectBiyoloji ve Biyokimya
dc.titleFluorescence-Based Screening Assays for the NAD(+)-Dependent Histone Deacetylase smSirt2 from Schistosoma mansoni
dc.typeMakale
dc.relation.journalJOURNAL OF BIOMOLECULAR SCREENING
dc.contributor.departmentUniversity of Freiburg , ,
dc.identifier.volume20
dc.identifier.issue1
dc.identifier.startpage112
dc.identifier.endpage121
dc.contributor.firstauthorID2199773


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