Formation of Cisplatin Adducts with the Epigenetically Relevant Nucleobase 5-Methylcytosine
2021-01-08
Annika Menke, Romeo C. A. Dubini, Peter Mayer,Petra Rovó, and Lena J. Daumann
With about 4 % abundance in the genome 5‐methylcytosine (5mC) is one of the most important epigenetic modifications. Change in DNA hypermethylation levels has even been linked to resistances to cisplatin treatment of cancer cells. This work aimed at the synthesis and full characterization of 5mC‐cisplatin adducts as well as for the examination of possible side‐reactions and transformations. We report the first X‐ray crystal structure of a cis‐[PtCl(5mC)(NH3)2]Cl complex and the formation of [PtCl(5mC)(NH3)2]+ and [PtCl(5mC)2(NH3)]+ with HR‐ESI mass spectrometry. Further, we explore complex formation and dynamics using 1H, 195Pt, and DOSY NMR spectroscopy. UV/Vis absorption and EPR spectroscopy also confirmed the formation of trace amounts of paramagnetic Pt‐blue species. In the process, a hemiprotonated 5mC dimer, 5mC‐5mCH+, reminiscent of the “i‐motif” in DNA tetramers, was structurally characterized.
Speaker: Prof. Dr. Thomas Carell
Ludwig-Maximilians-Universität München
Institut für Chemische Epigenetik (ICEM)
Department of Chemistry
Office:
Würmtalstrasse 201
81377 Munich
Germany
Mailing address:
Butenandtstr. 5 - 13
81377 Munich
Germany
Phone: +49 (0)89 2180-77750
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Secretary: Birgit Carell
Institute for Chemical Epigenetics Munich (ICEM)
Office:
Würmtalstrasse 201, Haus L - EG / Room: 007
81377 Munich
Germany
Mailing address:
Butenandtstr. 5 - 13
81377 Munich
Germany
Phone: +49 (0)89 2180-77751
Fax: +49 (0)89 2180-77881
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Prof. Dr. Lena Daumann
LMU Munich
Department of Chemistry
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House D, Room 3.075
81377 Munich, Germany
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Dr. Sabine Schneider
LMU Munich
Institute for Chemical Epigenetics
Butenandtstr. 5 - 13
House L
81377 Munich, Germany
Phone: +49 89 2180 77716
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Dr. Martin Sumser (Coordinator)
LMU Munich
Institute for Chemical Epigenetics
Butenandtstr. 5 - 13
House L
81377 Munich, Germany
Phone: +49 89 2180 77765
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