Poster abstracts
Poster number 57 submitted by Jun Jiang
Platination of nucleotides and nucleic acids by cisplatin and its derivatives
Jun Jiang (Department of Chemistry, Wayne State University), Bett Kimutai (Department of Chemistry, Wayne State University), Harjot Mann (Department of Chemistry, Wayne State University), Ahmed El-Moussa (Department of Chemistry, Wayne State University), Christine S. Chow (Department of Chemistry, Wayne State University)
Abstract:
Cisplatin and its derivatives have been successfully employed in the treatment of certain types of cancer. Coordination of platinum (II) to the N7 of G residues in DNA is established as the molecular mechanism resulting in cell death. Recent work has shown that RNA molecules are also susceptible towards platination reactions, and certain cisplatin derivatives, such as the amino-acid-linked Oplatin, demonstrate differential site preferences depending on the local RNA folding or nucleotide identities. Therefore, cisplatin and its derivatives are not only important as anticancer drugs, but may also serve as probes of secondary structures within large noncoding RNAs. Nuclear magnetic resonance (NMR) spectroscopy was employed to monitor reactions between NMPs (N = A, G, and C) and Oplatin, and the results were compared with those using the corresponding nucleosides. To determine the RNA product profiles following platination, enzyme digestions of the modified oligonucleotides coupled with mass spectrometry were employed. Together, the results from these two approaches are used to correlate the properties of coordination complexes and their reactivates towards different RNA residues or local structural elements, which is helpful for the design of new RNA-targeting drugs and probes.
Keywords: cisplatin, nucleotide, RNA