Mass spectrometry of <i>cis</i>‐diamminedichloroplatinum(II) adducts with the dinucleosidemonophosphates d(ApG), d(GpG) and d(TpC) in an ion trap

Hagemeister, Timo; Linscheid, Michael

doi:10.1002/jms.333

Cited by 32 publications

(25 citation statements)

References 23 publications

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“…The investigations of even longer oligomers showed d(ApGpGpT)‐Pt(DACH) as the most abundant one supporting the findings at dimer and trimer level (GG and GGT are the major formed adducts). The fragmentation of the oxaliplatin tetranucleotide adducts in the ion trap is similar to cisplatin adducts, but the fragments indicate that the oxaliplatin complexation is rather flexible and less stable in gas phase allowing rearrangements of the complexes. We observe a new gas phase interbase rearrangement (fragmentation pathways FB, FH and FI).…”

Section: Resultsmentioning

confidence: 92%

“…In most cases, the 5’ base is the adducted base, but a few exceptions exist. The most abundant adduct at the ICL dinucleotide level is the d(pGpC)‐Pt(DACH)‐d(pGpC), comparable to cisplatin‐DNA adducts . Adducts with modifications at the same ends of both DNA strands represented 85% of the total interstrand cross‐linked complexes with a distribution of G‐Pt‐G (0.56) to A‐Pt‐G (0.44).…”

Section: Resultsmentioning

confidence: 99%

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Structures of oxaliplatin‐oligonucleotide adducts from DNA

et al. 2012

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Oxaliplatin, [(1R,2R)-cyclohexane-1,2-diamine](ethanedioato-O,O')platinum(II) shows a great efficiency against colorectal cancer. Although the mode of action of oxaliplatin is not yet understood, it is commonly accepted that binding of oxaliplatin to DNA prevents DNA synthesis and alters protein to DNA binding. In order to elucidate the modified DNA-protein interaction and thus to understand the mechanisms leading to cellular misinterpretation of DNA information and apoptosis, we have identified the preferential binding sites and the dynamics of the oxaliplatin-DNA intrastrand and interstrand adducts at the oligomer level using high-performance liquid chromatography/electrospray ionization-tandem mass spectrometry (HPLC/ESI-MS/MS) and HPLC/inductively coupled plasma-MS for quantitative studies. We used a combination of benzonase, alkaline phosphatase and Nuclease S1 for digestion. This digestion procedure allows the study of platinated oligomeric nucleotides and more complex interstrand adducts. The digestion products were mostly chromatographically separated and characterized using HPLC/ESI-ion trap MS/MS experiments. We could show that the adducts to guanine and adenine are quite dynamic; that is, the ratios are changing for several days. In addition, the resulting adducts provide evidence for the action of the digesting enzymes and indicate that the adduct spectrum at the oligomeric level is different to that at the commonly studies dinucleotide level.

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Section: Resultsmentioning

confidence: 92%

Section: Resultsmentioning

confidence: 99%

Structures of oxaliplatin‐oligonucleotide adducts from DNA

et al. 2012

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“…In medicine, metal ions find broad therapeutic application on DNA, as cisplatin complexes and related drugs form DNA-adducts, which act as toxic agents in tumor tissue [6]. These drugs are widely applied even though the mechanism on the molecular level is not fully elucidated yet [7]. Furthermore, there are approaches to use metal ions as markers for improved diagnostic applications [8 -14].…”

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confidence: 99%

Investigation of metal-oligonucleotide complexes by nanoelectrospray tandem mass spectrometry in the positive mode

Monn

Schürch

2005

J. Am. Soc. Mass Spectrom.

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The formation and fragmentation of multiply metal-coordinated oligonucleotides was studied by nanoelectrospray tandem mass spectrometry in the positive ion mode. Fundamental aspects of the gas-phase behavior of metal-oligonucleotide complexes are revealed. The addition of transition metal ions, such as iron(II), iron(III), and zinc(II), leads to very stable metal-oligonucleotide complexes which show heavily altered fragmentation patterns in contrast to uncomplexed oligonucleotides. The site of metal ion complexation was located by collision-induced dissociation (CID) experiments. It was found that all three metal ions investigated predominantly coordinate to the central phosphate groups of the oligonucleotides. Furthermore, it is demonstrated that the fragmentation of such complexes depends highly upon the metal ion complexed as well as on the sequence of the nucleobases in the oligonucleotide. Besides their function as cofactors of proteins, especially in replication, transcription, and translation, they induce folding and crosslinking of nucleic acids and result in a stabilization of these structures. Such interaction can be highly specific, like the linkage of two guanines by cisplatin complexes, or unspecific, like backbone charge neutralization on a DNA double strand [1,2]. Likewise, metal ions are involved in the stabilization of RNA, ribozymes, and telomers [3][4][5]. In medicine, metal ions find broad therapeutic application on DNA, as cisplatin complexes and related drugs form DNA-adducts, which act as toxic agents in tumor tissue [6]. These drugs are widely applied even though the mechanism on the molecular level is not fully elucidated yet [7]. Furthermore, there are approaches to use metal ions as markers for improved diagnostic applications [8 -14]. The application of metal ions may even hold more potential, which can be taken advantage of once the interactions of metal ions with nucleic acid structures are better understood. Several NMR studies have been published with the aim of elucidating the metal ion binding pattern [15][16][17]. Although several approaches have been made to determine the coordination sites, no general rule on how metal ions bind to nucleic acid structures could be established yet.The interaction of metal ions with nucleic acids has also been investigated using mass spectrometry. In an early study, Christian et al. describe the influence of iron on oligonucleotides as matrix dependent [18]. Another study describes the influence of Mg 2ϩ , Na ϩ , and UO 2 2ϩ on oligonucleotides and demonstrates that the phosphodiester groups are considered the most probable binding sites. Additionally, it is reported that these metal ions bind preferentially to the central thymine region of the analyzed octa-and dodecamer [14].By exploring oligonucleotides with their phosphate groups completely occupied by alkali or earthalkali ions, Gross and coworkers observed that the product ion spectra of such metal complexed oligonucleotides differ significantly from the spectra of their uncomplexed analo...

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“…Again the structure analysis of the modified oligonucleotides was based on ESI/MSMS data, but quantitative data were only accessible via LC/ICP‐MS . In this study we used phosphorus again to quantify DNA adducts in order to show DNA repair of cross links (Figure )…”

Section: Applicationsmentioning

confidence: 99%

Molecules and elements for quantitative bioanalysis: The allure of using electrospray, MALDI, and ICP mass spectrometry side‐by‐side

Linscheid

2018

Mass Spectrometry Reviews

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To understand biological processes, not only reliable identification, but quantification of constituents in biological processes play a pivotal role. This is especially true for the proteome: protein quantification must follow protein identification, since sometimes minute changes in abundance tell the real tale. To obtain quantitative data, many sophisticated strategies using electrospray and MALDI mass spectrometry (MS) have been developed in recent years. All of them have advantages and limitations. Several years ago, we started to work on strategies, which are principally capable to overcome some of these limits. The fundamental idea is to use elemental signals as a measure for quantities. We began by replacing the radioactive P with the "cold" natural P to quantify modified nucleotides and phosphorylated peptides and proteins and later used tagging strategies for quantification of proteins more generally. To do this, we introduced Inductively Coupled Plasma Mass Spectrometry (ICP-MS) into the bioanalytical workflows, allowing not only reliable and sensitive detection but also quantification based on isotope dilution absolute measurements using poly-isotopic elements. The detection capability of ICP-MS becomes particularly attractive with heavy metals. The covalently bound proteins tags developed in our group are based on the well-known DOTA chelate complex (1,4,7,10-tetraazacyclododecane-N,N',N″,N‴-tetraacetic acid) carrying ions of lanthanoides as metal core. In this review, I will outline the development of this mutual assistance between molecular and elemental mass spectrometry and discuss the scope and limitations particularly of peptide and protein quantification. The lanthanoide tags provide low detection limits, but offer multiplexing capabilities due to the number of very similar lanthanoides and their isotopes. With isotope dilution comes previously unknown accuracy. Separation techniques such as electrophoresis and HPLC were used and just slightly adapted workflows, already in use for quantification in bioanalysis. Imaging mass spectrometry (MSI) with MALDI and laser ablation ICP-MS complemented the range of application in recent years.

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Mass spectrometry of cis‐diamminedichloroplatinum(II) adducts with the dinucleosidemonophosphates d(ApG), d(GpG) and d(TpC) in an ion trap

Cited by 32 publications

References 23 publications

Structures of oxaliplatin‐oligonucleotide adducts from DNA

Structures of oxaliplatin‐oligonucleotide adducts from DNA

Investigation of metal-oligonucleotide complexes by nanoelectrospray tandem mass spectrometry in the positive mode

Molecules and elements for quantitative bioanalysis: The allure of using electrospray, MALDI, and ICP mass spectrometry side‐by‐side

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