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dc.contributor.authorKirsch, Philine
dc.contributor.authorJakob, Valentin
dc.contributor.authorElgaher, Walid A M
dc.contributor.authorWalt, Christine
dc.contributor.authorOberhausen, Kevin
dc.contributor.authorSchulz, Thomas F
dc.contributor.authorEmpting, Martin
dc.date.accessioned2020-02-13T12:58:25Z
dc.date.available2020-02-13T12:58:25Z
dc.date.issued2020-01-24
dc.identifier.citationACS Chem Biol. 2020 Jan 24. doi: 10.1021/acschembio.9b00845.en_US
dc.identifier.issn1554-8937
dc.identifier.pmid31944659
dc.identifier.doi10.1021/acschembio.9b00845
dc.identifier.urihttp://hdl.handle.net/10033/622132
dc.description.abstractWith the aim to develop novel antiviral agents against Kaposi's Sarcoma Herpesvirus (KSHV), we are targeting the latency-associated nuclear antigen (LANA). This protein plays an important role in viral genome maintenance during latent infection. LANA has the ability to tether the viral genome to the host nucleosomes and, thus, ensures latent persistence of the viral genome in the host cells. By inhibition of the LANA-DNA interaction, we seek to eliminate or reduce the load of the viral DNA in the host. To achieve this goal, we screened our in-house library using a dedicated fluorescence polarization (FP)-based competition assay, which allows for the quantification of LANA-DNA-interaction inhibition by small organic molecules. We successfully identified three different compound classes capable of disrupting this protein-nucleic acid interaction. We characterized these compounds by IC50 dose-response evaluation and confirmed the compound-LANA interaction using surface plasmon resonance (SPR) spectroscopy. Furthermore, two of the three hit scaffolds showed only marginal cytotoxicity in two human cell lines. Finally, we conducted STD-NMR competition experiments with our new hit compounds and a previously described fragment-sized inhibitor. Based on these results, future compound linking approaches could serve as a promising strategy for further optimization studies in order to generate highly potent KSHV inhibitors.en_US
dc.language.isoenen_US
dc.publisherAmerican Chemical Society (ACS)en_US
dc.rightsAttribution-NonCommercial-ShareAlike 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.titleDiscovery of Novel Latency-Associated Nuclear Antigen Inhibitors as Antiviral Agents Against Kaposi's Sarcoma-Associated Herpesvirus.en_US
dc.typeArticleen_US
dc.contributor.departmentHIPS, Helmholtz-Institut für Pharmazeutische Forschung Saarland, Universitätscampus E8.1 66123 Saarbrücken, Germany.;HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany.en_US
dc.identifier.journalACS Chemical Biologyen_US
dc.source.journaltitleACS chemical biology


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