Ultrafast sequencing of oligodeoxyribonucleo tides by FAB-mass spectrometry

Grotjahn, Lutz; Frank, Ronald; Blöcker, Helmut

doi:10.1093/nar/10.15.4671

Cited by 117 publications

(31 citation statements)

References 7 publications

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“…T he gas-phase fragmentation of oligonucleotides has been studied during the past two decades, beginning with the early fast-atom bombardment studies by Grotjahn et al [1,2]. Introduction of the soft ionization methods electrospray ionization (ESI) and matrix assisted laser desorption/ionization (MALDI) in the early 90s increased the general emphasis on developing mass spectrometry for oligonucleotide research.…”

mentioning

confidence: 99%

RNA fragmentation in MALDI mass spectrometry studied by H/D-exchange: Mechanisms of general applicability to nucleic acids

Andersen

Kirpekar

Haselmann

2006

J. Am. Soc. Mass Spectrom.

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To reveal the gas-phase chemistry of RNA and DNA fragmentation during MALDI mass spectrometry in positive ion mode, we performed hydrogen/deuterium exchange on a series of RNA and DNA tetranucleotides and studied their fragmentation patterns on a highresolution MALDI TOF-TOF instrument. We were specifically interested in elucidating the remarkably different fragmentation behavior of RNA and DNA, i.e., the characteristic and abundant production of c-and y-ions from RNA versus a dominating generation of (a-B)-and w-ions from DNA analytes. The analysis yielded important information on all significant backbone cleavages as well as nucleobase losses. Based on this, we suggest common fragmentation mechanisms for RNA and DNA as well as an important RNA-specific reaction requiring a 2=-hydroxyl group, leading to c-and y-ions. The data is viewed and discussed in the context of previously published data to obtain a coherent picture of the fragmentation of singly protonated nucleic acids. (J Am Soc Mass Spectrom 2006, 17, 1353-1368

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confidence: 99%

RNA fragmentation in MALDI mass spectrometry studied by H/D-exchange: Mechanisms of general applicability to nucleic acids

Andersen

Kirpekar

Haselmann

2006

J. Am. Soc. Mass Spectrom.

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“…FAB was an improvement over 252 Cf PDMS with respect to the ease of sample preparation. Grotjahn et al (Grotjahn et al, 1982) used FAB-MS to sequence a decanucleotide, and later Cerny et al (Cerny et al, 1986) used collision induced dissociation (CID) to sequence dinucleotides and proposed a mechanism for base loss. The Cf-PD and FAB methods required rather significant sample quantities and were not effective for molecules over 4000 Da.…”

Section: Mass Spectrometry For Analysis Of Nucleic Acidsmentioning

confidence: 99%

Tandem mass spectrometry for characterization of covalent adducts of DNA with anticancer therapeutics

Silvestri

Brodbelt

2012

Mass Spectrometry Reviews

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The chemotherapeutic activities of many anticancer and antibacterial drugs arise from their interactions with nucleic acid substrates. Some of these ligands interact with DNA in a way that causes conformational changes or damage to the nucleic acid targets, ultimately altering recognition by key DNA-specific enzymes, interfering with DNA transcription or prohibiting replication, and terminating cell growth and proliferation. The design and synthesis of ligands that bind to nucleic acids remains a dynamic field in medicinal chemistry and pharmaceutical research. The quest for more selective and efficacious DNA-interactive anti-cancer chemotherapeutics has likewise catalyzed the need for sensitive analytical methods that can provide structural information about the nature of the resulting DNA adducts and provide insight into the mechanistic pathways of the DNA/drug interactions and the impact on the cellular processes in biological systems. This review focuses on the array of tandem mass spectrometric strategies developed and applied for characterization of covalent adducts formed between DNA and anti-cancer ligands.

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“…Excellent sensitivity and the formation of multiply charged molecular ions permit accurate mass determinations and facilitate the use of low mass range instruments for the analysis of high molecular weight compounds. Prior to the development of the electrospray technique, fast atom bombardment (FAB) was useful for the analysis of small oligomers (6)(7)(8); however, no ionization technique was available routinely for mass analysis of large oligomers. In the negative ion mode, FAB mass spectra contain an intense molecular ion (M-H)" and two series of fragment ions formed by the cleavage of the carbon-oxygen bond in the sugarphosphate backbone at the C3 1 or C5' positions on the ribose moiety.…”

Section: Fisons Instruments 55 Cherry Hill Drive Beverly Ma 01915mentioning

confidence: 99%

Application of Electrospray Ionization Mass Spectrometry to the Analysis of Oligodeoxynucleotides

Iden

Rieger

Torres

et al. 1996

ACS Symposium Series

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Electrospray mass spectrometry is a powerful technique for the analysis of oligodeoxynucleotides providing accurate molecular masses from the multiply charged negative ions formed by the electrospray volatilization/ionization process. Fragment ions are generally absent unless formed by secondary collisions near the exit of the source where pressures are relatively high. Use of the electrospray technique for the analysis of oligodeoxynucleotides is superior to other ionization techniques for verification of site-specific incorporation of modified deoxynucleotides, especially for oligomers containing more than ten deoxynucleotides where FAB/MS is not effective. ESI spectra may be generated on 10-100 picomoles of an oligomer on a single quadrupole mass spectrometer system, and mass accuracy of ±0.01% is attainable with careful calibration of the instrument. Spectra are presented for oligomers containing modified nucleobases and sugar moieties, as well as a hybrid DNA/RNA oligomer in which an O-methyl moiety is positioned at the 2'-position of adenosine. The technique is also effective for the elucidation of mechanisms by which unstable oligomers may disintegrate into unknown products, and the known sensitivity of 8-oxo-2-deoxyguanosine-containing oligomers to the postsynthetic ammonia deprotection procedure has been examined. ESI/MS was used to characterize the major products of oligomer decomposition. Deoxynucleotide sequence of an oligomer cannot be determined from the electrospray mass spectrum. However, MS/MS experiments were conducted on multiply charged oligodeoxynucleotide molecular ions generated by ESI on a triple quadrupole instrument. Product ion spectra from collision induced dissociation are complex, and product ions may differ in charge state from the precursor ion. However, families of ions were identified from which the sequence of the oligomer was verified.

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Ultrafast sequencing of oligodeoxyribonucleo tides by FAB-mass spectrometry

Cited by 117 publications

References 7 publications

RNA fragmentation in MALDI mass spectrometry studied by H/D-exchange: Mechanisms of general applicability to nucleic acids

RNA fragmentation in MALDI mass spectrometry studied by H/D-exchange: Mechanisms of general applicability to nucleic acids

Tandem mass spectrometry for characterization of covalent adducts of DNA with anticancer therapeutics

Application of Electrospray Ionization Mass Spectrometry to the Analysis of Oligodeoxynucleotides

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