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Clickable Cisplatin Derivatives as Versatile Tools to Probe the DNA Damage Response to Chemotherapy

Clickable Cisplatin Derivatives as Versatile Tools to Probe the DNA Damage Response to Chemotherapy

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MORETTON, Amandine, Jana SLYSKOVA, Marwan E. SIMAAN, Emili A. ARASA-VERGE, Mathilde MEYENBERG, Daniel Alonso CERRÓN INFANTES, Miriam M. UNTERLASS, Joanna I. LOIZOU, 2022. Clickable Cisplatin Derivatives as Versatile Tools to Probe the DNA Damage Response to Chemotherapy. In: Frontiers in Oncology. Frontiers Media. 12, 874201. eISSN 2234-943X. Available under: doi: 10.3389/fonc.2022.874201

@article{Moretton2022Click-57892, title={Clickable Cisplatin Derivatives as Versatile Tools to Probe the DNA Damage Response to Chemotherapy}, year={2022}, doi={10.3389/fonc.2022.874201}, volume={12}, journal={Frontiers in Oncology}, author={Moretton, Amandine and Slyskova, Jana and Simaan, Marwan E. and Arasa-Verge, Emili A. and Meyenberg, Mathilde and Cerrón Infantes, Daniel Alonso and Unterlass, Miriam M. and Loizou, Joanna I.}, note={Article Number: 874201} }

<rdf:RDF xmlns:dcterms="http://purl.org/dc/terms/" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:bibo="http://purl.org/ontology/bibo/" xmlns:dspace="http://digital-repositories.org/ontologies/dspace/0.1.0#" xmlns:foaf="http://xmlns.com/foaf/0.1/" xmlns:void="http://rdfs.org/ns/void#" xmlns:xsd="http://www.w3.org/2001/XMLSchema#" > <rdf:Description rdf:about="https://kops.uni-konstanz.de/rdf/resource/123456789/57892"> <dc:date rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2022-06-30T09:56:40Z</dc:date> <dc:contributor>Unterlass, Miriam M.</dc:contributor> <dc:creator>Arasa-Verge, Emili A.</dc:creator> <dcterms:available rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2022-06-30T09:56:40Z</dcterms:available> <dcterms:title>Clickable Cisplatin Derivatives as Versatile Tools to Probe the DNA Damage Response to Chemotherapy</dcterms:title> <dc:creator>Unterlass, Miriam M.</dc:creator> <dc:contributor>Slyskova, Jana</dc:contributor> <dcterms:abstract xml:lang="eng">Cisplatin induces DNA crosslinks that are highly cytotoxic. Hence, platinum complexes are frequently used in the treatment of a broad range of cancers. Efficiency of cisplatin treatment is limited by the tumor-specific DNA damage response to the generated lesions. We reasoned that better tools to investigate the repair of DNA crosslinks induced by cisplatin would therefore be highly useful in addressing drug limitations. Here, we synthesized a series of cisplatin derivatives that are compatible with click chemistry, thus allowing visualization and isolation of DNA-platinum crosslinks from cells to study cellular responses. We prioritized one alkyne and one azide Pt(II) derivative, Pt-alkyne-53 and Pt-azide-64, for further biological characterization. We demonstrate that both compounds bind DNA and generate DNA lesions and that the viability of treated cells depends on the active DNA repair machinery. We also show that the compounds are clickable with both a fluorescent probe as well as biotin, thus they can be visualized in cells, and their ability to induce crosslinks in genomic DNA can be quantified. Finally, we show that Pt-alkyne-53 can be used to identify DNA repair proteins that bind within its proximity to facilitate its removal from DNA. The compounds we report here can be used as valuable experimental tools to investigate the DNA damage response to platinum complexes and hence might shed light on mechanisms of chemoresistance.</dcterms:abstract> <dc:contributor>Simaan, Marwan E.</dc:contributor> <dspace:isPartOfCollection rdf:resource="https://kops.uni-konstanz.de/rdf/resource/123456789/29"/> <dc:rights>Attribution 4.0 International</dc:rights> <dc:creator>Simaan, Marwan E.</dc:creator> <dc:creator>Meyenberg, Mathilde</dc:creator> <foaf:homepage rdf:resource="http://localhost:8080/jspui"/> <dc:contributor>Moretton, Amandine</dc:contributor> <dc:contributor>Arasa-Verge, Emili A.</dc:contributor> <dc:creator>Cerrón Infantes, Daniel Alonso</dc:creator> <dcterms:hasPart rdf:resource="https://kops.uni-konstanz.de/bitstream/123456789/57892/1/Moretton_2-thibq31o8vaa3.pdf"/> <dspace:hasBitstream rdf:resource="https://kops.uni-konstanz.de/bitstream/123456789/57892/1/Moretton_2-thibq31o8vaa3.pdf"/> <dcterms:issued>2022</dcterms:issued> <dcterms:isPartOf rdf:resource="https://kops.uni-konstanz.de/rdf/resource/123456789/29"/> <dc:contributor>Cerrón Infantes, Daniel Alonso</dc:contributor> <void:sparqlEndpoint rdf:resource="http://localhost/fuseki/dspace/sparql"/> <dc:contributor>Meyenberg, Mathilde</dc:contributor> <dcterms:rights rdf:resource="http://creativecommons.org/licenses/by/4.0/"/> <dc:creator>Slyskova, Jana</dc:creator> <dc:language>eng</dc:language> <bibo:uri rdf:resource="https://kops.uni-konstanz.de/handle/123456789/57892"/> <dc:creator>Loizou, Joanna I.</dc:creator> <dc:contributor>Loizou, Joanna I.</dc:contributor> <dc:creator>Moretton, Amandine</dc:creator> </rdf:Description> </rdf:RDF>

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