OMA and OPA—Software-Supported Mass Spectra Analysis of Native and Modified Nucleic Acids

AbstractThe platform-independent software package consisting of the oligonucleotide mass assembler (OMA) and the oligonucleotide peak analyzer (OPA) was created to support the analysis of oligonucleotide mass spectra. It calculates all theoretically possible fragments of a given input sequence and annotates it to an experimental spectrum, thus, saving a large amount of manual processing time. The software performs analysis of precursor and product ion spectra of oligonucleotides and their analogues comprising user-defined modifications of the backbone, the nucleobases, or the sugar moiety, as well as adducts with metal ions or drugs. The ability to expand the library of building blocks and to implement individual structural variations makes it extremely useful for supporting the analysis of therapeutically active compounds. The functionality of the software tool is demonstrated on the examples of a platinated double-stranded oligonucleotide and a modified RNA sequence. Experiments also reveal the unique dissociation behavior of platinated higher-order DNA structures.

[1]  S. Schürch,et al.  Tandem Mass Spectrometry of Modified and Platinated Oligoribonucleotides , 2011, Journal of the American Society for Mass Spectrometry.

[2]  Gary L. Glish,et al.  Tandem Mass Spectrometry of Small, Multiply Charged Oligonucleotides , 1992, Journal of the American Society for Mass Spectrometry.

[3]  M. Gross,et al.  Gas-phase stability of double-stranded oligodeoxynucleotides and their noncovalent complexes with DNA-binding drugs as revealed by collisional activation in an ion trap , 2000, Journal of the American Society for Mass Spectrometry.

[4]  C. Huber,et al.  Comparative sequencing of nucleic acids by liquid chromatography-tandem mass spectrometry. , 2002, Analytical chemistry.

[5]  M. Manoharan,et al.  An automated algorithm for sequence confirmation of chemically modified oligonucleotides by tandem mass spectrometry. , 2010, Analytical biochemistry.

[6]  B. Keppler,et al.  High resolution mass spectrometry for studying the interactions of cisplatin with oligonucleotides. , 2008, Inorganic chemistry.

[7]  S. A. McLuckey,et al.  Accumulation and storage of ionized duplex DNA molecules in a quadrupole ion trap. , 1994, Analytical chemistry.

[8]  C. G. Edmonds,et al.  Observation of a small oligonucleotide duplex by electrospray ionization mass spectrometry , 1993 .

[9]  J. Rozenski,et al.  Interpretation of oligonucleotide mass spectra for determination of sequence using electrospray ionization and tandem mass spectrometry. , 1996, Analytical chemistry.

[10]  Jef Rozenski,et al.  SOS: A simple interactive program for ab initio oligonucleotide sequencing by mass spectrometry , 2002, Journal of the American Society for Mass Spectrometry.

[11]  S. A. McLuckey,et al.  Gas-phase fragmentation of oligonucleotide ions , 2004 .

[12]  Irwin D Kuntz,et al.  The collaboratory for MS3D: a new cyberinfrastructure for the structural elucidation of biological macromolecules and their assemblies using mass spectrometry-based approaches. , 2008, Journal of proteome research.

[13]  M. Gross,et al.  Structure and fragmentation mechanisms of isomeric T-rich oligodeoxynucleotides: A comparison of four tandem mass spectrometric methods , 1998, Journal of the American Society for Mass Spectrometry.

[14]  F. Kirpekar,et al.  RNA fragmentation in MALDI mass spectrometry studied by H/D-exchange: Mechanisms of general applicability to nucleic acids , 2006, Journal of the American Society for Mass Spectrometry.

[15]  S. Schürch,et al.  The influence of cisplatin on the gas-phase dissociation of oligonucleotides studied by electrospray ionization tandem mass spectrometry , 2009, Journal of the American Society for Mass Spectrometry.

[16]  F. McLafferty,et al.  Accurate base composition of double-strand DNA by mass spectrometry , 1996, Journal of the American Society for Mass Spectrometry.

[17]  S. Schürch,et al.  Gas-phase dissociation of oligoribonucleotides and their analogs studied by electrospray ionization tandem mass spectrometry , 2005, Journal of the American Society for Mass Spectrometry.

[18]  B. Ganem,et al.  Detection of oligonucleotide duplex forms by ion-spray mass spectrometry , 1993 .

[19]  B. Keppler,et al.  Ruthenium versus platinum: interactions of anticancer metallodrugs with duplex oligonucleotides characterised by electrospray ionisation mass spectrometry , 2010, JBIC Journal of Biological Inorganic Chemistry.

[20]  C. Leumann,et al.  Electrospray tandem mass spectrometry of mixed-sequence RNA/DNA oligonucleotides , 2002, Journal of the American Society for Mass Spectrometry.

[21]  Malin M. Young,et al.  Top-down characterization of nucleic acids modified by structural probes using high-resolution tandem mass spectrometry and automated data interpretation. , 2004, Analytical chemistry.

[22]  K. Bleicher,et al.  Analysis of double-stranded oligonucleotides by electrospray mass spectrometry. , 1994, Analytical chemistry.