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• W2017695945 abstract "Therapeutic approaches for treatment of various diseases aim at the interruption of transcription or translation. Modified oligonucleotides, such as 2′-O-methyl- and methylphosphonate-derivatives, exhibit high resistance against cellular nucleases, thus rendering application for, e.g., antigene or antisense purposes possible. Other approaches are based on administration of cross-linking agents, such as cis-diamminedichloroplatinum(II) (cisplatin, DDP), which is still the most widely used anticancer drug worldwide. Due to the formation of 1,2-intrastrand cross links at adjacent guanines, replication of the double-strand is disturbed, thus resulting in significant cytotoxicity. Evidence for the gas-phase dissociation mechanism of platinated RNA is given, based on nano-electrospray ionization high-resolution multistage tandem mass spectrometry (MSn). Confirmation was found by investigating the fragmentation pattern of platinated and unplatinated 2′-methoxy oligoribonucleotide hexamers and their corresponding methylphosphonate derivatives. Platinated 2′-methoxy oligoribonucleotides exhibit a similar gas-phase dissociation behavior as the corresponding DNA and RNA sequences, with the 3′–C–O bond adjacent to the vicinal guanines being cleaved preferentially, leading to wx-ion formation. By examination of the corresponding platinated methylphosphonate derivatives of the 2′-methoxy oligoribonucleotides, the key role of the negatively charged phosphate oxygen atoms in direct proximity to the guanines was proven. The significant alteration of fragmentation due to platination is demonstrated by comparison of the fragment ion patterns of unplatinated and platinated 2′-O-methyl- and 2′-O-methyl methylphosphonate oligoribonucleotides, and the results obtained by H/D exchange experiments." @default.
• W2017695945 created "2016-06-24" @default.
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• W2017695945 date "2011-03-23" @default.
• W2017695945 modified "2023-09-25" @default.
• W2017695945 title "Tandem Mass Spectrometry of Modified and Platinated Oligoribonucleotides" @default.
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• W2017695945 doi "https://doi.org/10.1007/s13361-011-0106-z" @default.
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