181630-15-9Relevant articles and documents
Chromatin Regulates Genome Targeting with Cisplatin
Zacharioudakis, Emmanouil,Agarwal, Poonam,Bartoli, Alexandra,Abell, Nathan,Kunalingam, Lavaniya,Bergoglio, Valérie,Xhemalce, Blerta,Miller, Kyle M.,Rodriguez, Rapha?l
, p. 6483 - 6487 (2017)
Cisplatin derivatives can form various types of DNA lesions (DNA-Pt) and trigger pleiotropic DNA damage responses. Here, we report a strategy to visualize DNA-Pt with high resolution, taking advantage of a novel azide-containing derivative of cisplatin we named APPA, a cellular pre-extraction protocol and the labeling of DNA-Pt by means of click chemistry in cells. Our investigation revealed that pretreating cells with the histone deacetylase (HDAC) inhibitor SAHA led to detectable clusters of DNA-Pt that colocalized with the ubiquitin ligase RAD18 and the replication protein PCNA. Consistent with activation of translesion synthesis (TLS) under these conditions, SAHA and cisplatin cotreatment promoted focal accumulation of the low-fidelity polymerase Polη that also colocalized with PCNA. Remarkably, these cotreatments synergistically triggered mono-ubiquitination of PCNA and apoptosis in a RAD18-dependent manner. Our data provide evidence for a role of chromatin in regulating genome targeting with cisplatin derivatives and associated cellular responses.
VISUAL DETECTION OF PLATINATED DNA LESIONS FROM A CLICKABLE CISPLATIN PROBE USED AS DIAGNOSTIC TOOL OR TO IDENTIFY SYNERGISTIC TREATMENTS
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Page/Page column 22; 23, (2017/07/06)
The present invention relates to a new compound for visualizing DNA-platinum crosslink, and its use as a research tool and in screening method for identifying candidate drug to be used in combination with platinating compounds such as cisplatin, carboplatin, and oxaliplatin. Formulae (I), (II) or (III). The project leading to this application has received funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation program (grant agreement No [647973]).
Photoactive trans ammine/amine diazido platinum(IV) complexes
Mackay, Fiona S.,Moggach, Stephen A.,Collins, Anna,Parsons, Simon,Sadler, Peter J.
, p. 811 - 819 (2009/05/30)
The synthesis and characterisation of eight new octahedral PtIV complexes of the type trans,trans,trans-[Pt(N3)2(OH)2(NH3)(Am)] where Am = methylamine (2), ethylamine (4), thiazole (6), 2-picoline (8)