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Fragmentation Reactions of Nucleic Acid Ions in the Gas Phase

  • Yang Gao
  • Scott A. McLuckey
Chapter
Part of the Physical Chemistry in Action book series (PCIA)

Abstract

This chapter summarizes literature describing the gas-phase fragmentation of nucleic acid ions under a variety of reaction conditions. Specifically, the phenomenology of gas-phase dissociation of nucleic acid ions is determined by ion type, charge state, the energy deposition method, and the fragmentation reaction timescale. Various proposed mechanisms are summarized. The chapter is organized by dissociation method. For the most extensively studied collision-induced dissociation (CID), the literature is subcategorized by analyte and ion type. In many cases, no single fragmentation mechanism can account for all the reported products. This suggests that multiple dissociation mechanisms can contribute, depending on ion type, ion charge state, and reaction conditions.

Keywords

Nucleic acids Gas-phase fragmentation Electrospray ionization Matrix-assisted laser desorption/ionization collision-induced dissociation Infrared multiphoton dissociation Ultraviolet photodissociation Electron photodetachment dissociation 

Abbreviations

BIRD

Blackbody infrared radiative dissociation

CID

Collision-induced dissociation

DNA

Deoxyribonucleotide

DR

Double resonance

ECD

Electron capture dissociation

EDD

Electron detachment dissociation

EPD

Electron photodetachment dissociation

ESI

Electrospray ionization

ETD

Electron transfer dissociation

ETcaD

Electron transfer collision-activated dissociation

ET-IRMPD

Electron transfer-infrared multiphoton dissociation

ET-UVPD

Electron transfer-ultraviolet photodissociation

FAB

Fast atom bombardment

FTICR

Fourier transform ion cyclotron resonance

IP

Ionization potential

IR

Infrared

IRMPD

Infrared multiphoton dissociation

LNA

Locked nucleic acid

MALDI

Matrix-assisted laser desorption/ionization

MBO

Mixed-backbone oligonucleotide

MP

Methylphosphonate

MS

Mass spectrometer/mass spectrometry

NETD

Negative electron transfer dissociation

niECD

Negative ion electron capture dissociation

NS

Nozzle-skimmer

PA

Proton affinity

PD

Plasma desorption

PS

Phosphorothioate

PSD

Post-source decay

Q-TOF

Quadrupole/time-of-flight tandem mass spectrometer

rf

Radiofrequency

RNA

Ribonucleotide

RNAi

RNA interference

SID

Surface-induced dissociation

SNP

Single nucleotide polymorphisms

SORI

Sustained off-resonance irradiation

TOF

Time-of-flight

TOF/TOF

Tandem time-of-flight

UV

Ultraviolet

UVPD

Ultraviolet photodissociation

References

  1. 1.
    Fenn J, Mann M, Meng C, Wong S, Whitehouse C (1989) Electrospray ionization for mass-spectrometry of large biomolecules. Science 246:64–71Google Scholar
  2. 2.
    Hillenkamp F, Karas M (1991) Matrix-assisted laser desorption/ionization mass spectrometry of biopolymers. Anal Chem 63:A1193–A1202Google Scholar
  3. 3.
    Tabb D, Smith L, Breci L, Wysocki V, Lin D, Yates J (2003) Statistical characterization of ion trap tandem mass spectra from doubly charged tryptic peptides. Anal Chem 75:1155–1163Google Scholar
  4. 4.
    Breci L, Tabb D, Yates J, Wysocki V (2003) Cleavage N-terminal to proline: analysis of a database of peptide tandem mass spectra. Anal Chem 75:1963–1972Google Scholar
  5. 5.
    Huang Y, Triscari JM, Pasa-Tolic L, Anderson GA, Lipton MS, Smith RD, Wysocki VH (2004) Dissociation behavior of doubly-charged tryptic peptides: correlation of gas-phase cleavage abundance with Ramachandran plots. J Am Chem Soc 126:3034–3035Google Scholar
  6. 6.
    McLafferty FW (2001) Tandem mass spectrometric analysis of complex biological mixtures. Int J Mass Spectrom 212:81–87Google Scholar
  7. 7.
    Stephenson JL, McLuckey SA, Reid GE, Wells JM, Bundy JL (2002) Ion/ion chemistry as a top-down approach for protein analysis. Curr Opin Biotechnol 13:57–64Google Scholar
  8. 8.
    Reid GE, McLuckey SA (2002) ‘Top down’ protein characterization via tandem mass spectrometry. J Mass Spectrom 37:663–675Google Scholar
  9. 9.
    Harvey DJ (1996) Matrix-assisted laser desorption ionization mass spectrometry of oligosaccharides and glycoconjugates. J Chromatogr A 720:429–446Google Scholar
  10. 10.
    Zaia J (2004) Mass spectrometry of oligosaccharides. Mass Spectrom Rev 23:161–227Google Scholar
  11. 11.
    Nordhoff E, Kirpekar F, Roepstorff P (1996) Mass spectrometry of nucleic acids. Mass Spectrom Rev 15:67–138Google Scholar
  12. 12.
    Murray KK (1996) DNA sequencing by mass spectrometry. J Mass Spectrom 31:1203–1215Google Scholar
  13. 13.
    Muddiman DC, Smith RD (1998) Sequencing and characterization of larger oligonucleotides by electrospray ionization fourier transform ion cyclotron resonance mass spectrometry. Rev Anal Chem 12:1–68Google Scholar
  14. 14.
    Wu J, McLuckey SA (2004) Gas-phase fragmentation of oligonucleotide ions. Int J Mass Spectrom 237:197–241Google Scholar
  15. 15.
    Grotjahn L, Frank R, Blocker H (1982) Ultrafast sequencing of oligodeoxyribonucleotides by FAB-MASS spectrometry. Nucleic Acids Res 10:4671–4678Google Scholar
  16. 16.
    Grotjahn L, Blocker H, Frank R (1985) Mass spectroscopic sequence-analysis of oligonucleotides. Biomed Mass Spectrom 12:514–524Google Scholar
  17. 17.
    Cerny RL, Tomer KB, Gross ML, Grotjahn L (1987) Fast-atom bombardment combined with mass spectrometry for determining structures of small oligonucleotides. Anal Biochem 165:175–182Google Scholar
  18. 18.
    Cerny RL, Gross ML, Grotjahn L (1986) Fast-atom bombardment combined with tandem mass spectrometry for the study of dinucleotides. Anal Biochem 156:424–435Google Scholar
  19. 19.
    Viari A, Ballini JP, Vigny P, Shire D, Dousset P (1987) CF-252-Plasma desorption mass-spectrometry of oligonucleotides. 3. Sequence-analysis of unprotected tri-deoxyribonucleoside diphosphates by CF-252-plasma desorption mass-spectrometry. Biomed Environ Mass Spectrom 14:83–90Google Scholar
  20. 20.
    Nordhoff E, Karas M, Cramer R, Hahner S, Hillenkamp F, Kirpekar F, Lezius A, Muth J, Meier C, Engels JW (1995) Direct mass spectrometric sequencing of low-picomole amounts of oligodeoxynucleotides with up to 21 bases by matrix-assisted laser desorption/ionization mass spectrometry. J Mass Spectrom 30:99–112Google Scholar
  21. 21.
    McLuckey SA, Van Berkel GJ, Glish GL (1992) Tandem mass spectrometry of small, multiply charged oligonucleotides. J Am Soc Mass Spectrom 3:60–70Google Scholar
  22. 22.
    McLuckey SA, Mentinova M (2011) Ion/neutral, ion/electron, ion/photon, and ion/ion interactions in tandem mass spectrometry: do we need them all? Are they enough? J Am Soc Mass Spectrom 22:3–12Google Scholar
  23. 23.
    McLuckey SA (1992) Principles of collisional activation in analytical mass spectrometry. J Am Soc Mass Spectrom 3:599–614Google Scholar
  24. 24.
    Wells JM, McLuckey SA (2005) Collision-induced dissociation (cid) of peptides and proteins. Methods Enzymol 402:148–185Google Scholar
  25. 25.
    Limbach PA (1996) Indirect mass spectrometric methods for characterizing and sequencing oligonucleotides. Mass Spectrom Rev 15:297–336Google Scholar
  26. 26.
    Burlingame AL, Boyd RK, Gaskell SJ (1998) Mass spectrometry. Anal Chem 70:647R–716RGoogle Scholar
  27. 27.
    McLuckey SA, Stephenson JL, O’Hair RAJ (1997) Decompositions of odd- and even-electron anions derived from deoxy-polyadenylates. J Am Soc Mass Spectrom 8:148–154Google Scholar
  28. 28.
    McLuckey SA, Habibi-Goudarzi S (1993) Decompositions of multiply charged oligonucleotide anions. J Am Chem Soc 115:12085–12095Google Scholar
  29. 29.
    McLuckey SA, Habibi-Goudarzi S (1994) Ion trap tandem mass spectrometry applied to small multiply charged oligonucleotides with a modified base. J Am Soc Mass Spectrom 5:740–747Google Scholar
  30. 30.
    Habibi-Goudarzi S, McLuckey SA (1995) Ion trap collisional activation of the deprotonated deoxymononucleoside and deoxydinucleoside monophosphates. J Am Soc Mass Spectrom 6:102–113Google Scholar
  31. 31.
    McLuckey SA, Vaidyanathan G, Habibi-Goudarzi S (1995) Charged vs. neutral nucleobase loss from multiply charged oligonucleotide anions. J Mass Spectrom 30:1222–1229Google Scholar
  32. 32.
    McLuckey SA, Vaidyanathan G (1997) Charge state effects in the decompositions of single-nucleobase oligonucleotide polyanions. J Mass Spectrom Ion Process 162:1–16Google Scholar
  33. 33.
    Barry JP, Vouros P, Van Schepdael A, Law SJ (1995) Mass and sequence verification of modified oligonucleotides using electrospray tandem mass spectrometry. J Mass Spectrom 30:993–1006Google Scholar
  34. 34.
    Wolter MA, Engels JW (1995) Nanoelectrospray mass spectrometry mass spectrometry for the analysis of modified oligoribonucleotides. Eur Mass Spectrom 1:583–590Google Scholar
  35. 35.
    Gentil E, Banoub J (1996) Characterization and differentiation of isomeric self-complementary DNA oligomers by electrospray tandem mass spectrometry. J Mass Spectrom 31:83–94Google Scholar
  36. 36.
    Boschenok J, Sheil MM (1996) Electrospray tandem mass spectrometry of nucleotides. Rapid Commun Mass Spectrom 10:144–149Google Scholar
  37. 37.
    Ho YH, Kebarle P (1997) Studies of the dissociation mechanisms of deprotonated mononucleotides by energy resolved collision-induced dissociation. Int J Mass Spectrom 165:433–455Google Scholar
  38. 38.
    Little DP, Chorush RA, Speir JP, Senko MW, Kelleher NL, McLafferty FW (1994) Rapid sequencing of oligonucleotides by high-resolution mass spectrometry. J Am Chem Soc 116:4893–4897Google Scholar
  39. 39.
    Little DP, McLafferty FW (1995) Sequencing 50-mer DNAs using electrospray tandem mass spectrometry and complementary fragmentation methods. J Am Chem Soc 117:6783–6784Google Scholar
  40. 40.
    Little DP, Aaserud DJ, Valaskovic GA, McLafferty FW (1996) Sequence information from 42-108-mer DNAs (complete for a 50-mer) by tandem mass spectrometry. J Am Chem Soc 118:9352–9359Google Scholar
  41. 41.
    Rodgers MT, Campbell S, Marzluff EM, Beauchamp JL (1994) Low-energy collision-induced dissociation of deprotonated dinucleotides: determination of the energetically favored dissociation pathways and the relative acidities of the nucleic acid bases. Int J Mass Spectrom Ion Process 137:121–149Google Scholar
  42. 42.
    Vrkic AK, O’Hair RAJ, Foote S (2000) Fragmentation reactions of all 64 deprotonated trinucleotide and 16 mixed base tetranucleotide anions via tandem mass spectrometry in an ion trap. Aust J Chem 53:307–319Google Scholar
  43. 43.
    Sidona G, Uccella N, Weclawek K (1982) Structure determination of isomeric oligodeoxynucleotide salts by fast-atom bombardment mass-spectrometry. J Chem Res Synop 1982:184–185Google Scholar
  44. 44.
    Crain PF, Gregson JM, McCloskey JA, Nelson CC, Peltier JM, Phillips DR, Pomerantz SC (1996) Reddy, D.M. In: Burlingame AL, Carr SA (eds) Mass spectrometry in the biological sciences. Humana Press, Totowa, NJ, p 497Google Scholar
  45. 45.
    Bartlett MG, McCloskey JA, Manalili S, Griffey RH (1996) The effect of backbone charge on the collision-induced dissociation of oligonucleotides. J Mass Spectrom 31:1277–1283Google Scholar
  46. 46.
    Doktycz MJ, Habibi-Goudarzi S, McLuckey SA (1994) Accumulation and storage of ionized duplex DNA molecules in a quadrupole ion trap. Anal Chem 66:3416–3422Google Scholar
  47. 47.
    Aaserud DJ, Kelleher NL, Little DP, McLafferty FW (1996) Accurate base composition of double-strand DNA by mass spectrometry. J Am Soc Mass Spectrom 7:1266–1269Google Scholar
  48. 48.
    McLafferty FW, Aaserud DJ, Guan ZQ, Little DP, Kelleher NL (1997) Double stranded DNA sequencing by tandem mass spectrometry. Int J Mass Spectrom 165:457–466Google Scholar
  49. 49.
    Schnier PD, Klassen JS, Strittmatter EE, Williams ER (1998) Activation energies for dissociation of double strand oligonucleotide anions: evidence for Watson-Crick base pairing in vacuo. J Am Chem Soc 120:9605–9613Google Scholar
  50. 50.
    Gabelica V, De Pauw E (2001) Comparison between solution-phase stability and gas-phase kinetic stability of oligodeoxynucleotide duplexes. J Mass Spectrom 36:397–402Google Scholar
  51. 51.
    Gabelica V, De Pauw E (2002) Collision-induced dissociation of 16-mer DNA duplexes with various sequences: evidence for conservation of the double helix conformation in the gas phase. Int J Mass Spectrom 219:151–159Google Scholar
  52. 52.
    Gabelica V, De Pauw E (2002) Comparison of the collision-induced dissociation of duplex DNA at different collision regimes: evidence for a multistep dissociation mechanism. J Am Soc Mass Spectrom 13:91–98Google Scholar
  53. 53.
    Ganem B, Li YT, Henion JD (1993) Detection of oligonucleotide duplex forms by ion-spray mass-spectrometry. Tetrahedron Lett 34:1445–1448Google Scholar
  54. 54.
    Bayer E, Bauer T, Schmeer K, Bleicher K, Maler M, Gaus HJ (1994) Analysis of double-stranded oligonucleotides by electrospray mass-spectrometry. Anal Chem 66:3858–3863Google Scholar
  55. 55.
    Ding JM, Anderegg RJ (1995) Specific and nonspecific dimer formation in the electrospray-ionization mass-spectrometry of oligonucleotides. J Am Soc Mass Spectrom 6:159–164Google Scholar
  56. 56.
    Greig MJ, Gaus HJ, Griffey RH (1996) Negative ionization micro electrospray mass spectrometry of oligonucleotides and their complexes. Rapid Commun Mass Spectrom 10:47–50Google Scholar
  57. 57.
    Madsen JA, Brodbelt JS (2010) Asymmetric charge partitioning upon dissociation of DNA duplexes. J Am Soc Mass Spectrom 21:1144–1150Google Scholar
  58. 58.
    Wan KX, Gross ML, Shibue T (2000) Gas-phase stability of double-stranded oligodeoxynucleotides and their noncovalent complexes with DNA-binding drugs as revealed by collisional activation in an ion trap. J Am Soc Mass Spectrom 11:450–457Google Scholar
  59. 59.
    Phillips DR, McCloskey JA (1993) A comprehensive study of the low-energy collision-induced dissociation of dinucleoside monophosphates. Int J Mass Spectrom Ion Process 128:61–82Google Scholar
  60. 60.
    Wang Z, Wan KX, Ramanathan R, Taylor JS, Gross ML (1998) Structure and fragmentation mechanisms of isomeric T-rich oligodeoxynucleotides: a comparison of four tandem mass spectrometric methods. J Am Soc Mass Spectrom 9:683–691Google Scholar
  61. 61.
    Wan KX, Gross J, Hillenkamp F, Gross ML (2001) Fragmentation mechanisms of oligodeoxynucleotides studied by H/D exchange and electrospray ionization tandem mass spectrometry. J Am Soc Mass Spectrom 12:193–205Google Scholar
  62. 62.
    Wan KX, Gross ML (2001) Fragmentation mechanisms of oligodeoxynucleotides: effects of replacing phosphates with methylphosphonates and thymines with other bases in T-rich sequences. J Am Soc Mass Spectrom 12:580–589Google Scholar
  63. 63.
    Vrkic AK, O’Hair RAJ, Foote S, Reid GE (2000) Fragmentation reactions of all 64 protonated trimer oligodeoxynucleotides and 16 mixed base tetramer oligodeoxynucleotides via tandem mass spectrometry in an ion trap. Int J Mass Spectrom 194:145–164Google Scholar
  64. 64.
    Wang PP, Bartlett MG, Martin LB (1997) Electrospray collision-induced dissociation mass spectra of positively charged oligonucleotides. Rapid Commun Mass Spectrom 11:846–856Google Scholar
  65. 65.
    Ni JS, Mathews MAA, McCloskey JA (1997) Collision-induced dissociation of polyprotonated oligonucleotides produced by electrospray ionization. Rapid Commun Mass Spectrom 11:535–540Google Scholar
  66. 66.
    Weimann A, Iannitti-Tito P, Sheil MM (2000) Characterisation of product ions in high-energy tandem mass spectra of protonated oligonucleotides formed by electrospray ionization. Int J Mass Spectrom 194:269–288Google Scholar
  67. 67.
    Rodgers MT, Campbell S, Marzluff EM, Beauchamp JL (1995) Site-specific protonation directs low-energy dissociation pathways of dinucleotides in the gas phase. Int J Mass Spectrom Ion Process 148:1–23Google Scholar
  68. 68.
    Dongre AR, Jones JL, Somogyi A, Wysocki VH (1996) Influence of peptide composition, gas-phase basicity, and chemical modification on fragmentation efficiency: evidence for the mobile proton model. J Am Chem Soc 118:8365–8374Google Scholar
  69. 69.
    Harrison AG, Yalcin T (1997) Proton mobility in protonated amino acids and peptides. Int J Mass Spectrom Ion Process 165:339–347Google Scholar
  70. 70.
    Schürch S, Bernal-Mendez E, Leumann CJ (2002) Electrospray tandem mass spectrometry of mixed-sequence RNA/DNA oligonucleotides. J Am Soc Mass Spectrom 13:936–945Google Scholar
  71. 71.
    Tromp JM, Schürch S (2005) Gas-phase dissociation of oligoribonucleotides and their analoges studied by electrospray ionization tandem mass spectrometry. J Am Soc Mass Spectrom 16:1262–1268Google Scholar
  72. 72.
    Tang W, Zhu L, Smith LM (1997) Controlling DNA fragmentation in MALDI-MS by chemical modification. Anal Chem 69:302–312Google Scholar
  73. 73.
    Huang T-Y, Kharlamova A, Liu J, McLuckey SA (2008) Ion trap collision-induced dissociation of multiply deprotonated RNA: c/y-ions versus (a-B)/w-ions. J Am Soc Mass Spectrom 19:1832–1840Google Scholar
  74. 74.
    Huang T-Y, Liu J, Liang X, Hodges BDM, McLuckey SA (2008) Collision-induced dissociation of intact duplex and single-stranded siRNA anions. Anal Chem 80:8501–8508Google Scholar
  75. 75.
    Kirpekar F, Krogh TN (2001) RNA fragmentation studied in a matric-assisted laser desorption/ionization tandem quadrupole/orthogonal time-of-flight mass spectrometer. Rapid Commun Mass Spectrom 15:8–14Google Scholar
  76. 76.
    Andersen TE, Kirpekar F, Haselmann KF (2006) RNA fragmentation in MALDI mass spectrometry studied by H/D-exchange: mechanisms of general applicability to nucleic acids. J Am Soc Mass Spectrom 17:1353–1368Google Scholar
  77. 77.
    Gross J, Leisner A, Hillenkamp F, Hahner S, Karas M, Schafer J, Lutzenkirchen F, Hordhoff E (1998) Investigations of the metastable decay of DNA under ultraviolet matrix-assisted laser desorption/ionization conditions with post-source decay analysis and hydrogen/deuterium exchange. J Am Soc Mass Spectrom 9:866–878Google Scholar
  78. 78.
    Horton HR, Moran LA, Ochs RS, Rawn JD, Scrimgeour KG (2002) Principles of biochemistry, 3rd edn. Prentice-Hall, Upper Saddle River, NJ, pp 605–607Google Scholar
  79. 79.
    Goodchild J (2004) Oligonucleotide therapeutics: 25 years agrowing. Curr Opin Mol Ther 6:120–128Google Scholar
  80. 80.
    Opalinska JB, Gewirtz AM (2002) Nucleic acid therapeutics: basic principles and recent applications. Nat Rev Drug Discov 1:503–514Google Scholar
  81. 81.
    Raal FJ, Santos RD, Blom DJ, Marais AD, Charng MJ, Cromwell WC, Lachmann RH, Gaudet D, Tan JL, Chasan-Taber S, Tribble DL, Flaim JD, Crooke ST (2010) Mipomersen, an apolipoprotein B synthesis inhibitor, for lowering of LDL cholesterol concentrations in patients with homozygous familial hypercholesterolaemia: a randomised, double-blind, placebo-controlled trial. Lancet 375:998–1006Google Scholar
  82. 82.
    Brody EN, Gold L (2000) Aptamers as therapeutic and diagnostic agents. J Biotechnol 74:5–13Google Scholar
  83. 83.
    Chiu Y-L, Rana TM (2009) siRNA function in RNAi: a chemical modification analysis. RNA 9:1034–1048Google Scholar
  84. 84.
    Butora G, Kenski DM, Cooper AJ, Fu WL, Qi N, Li JJ, Flanagan WM, Davies IW (2005) Potent and persistent in vivo anti-HBV activity of chemically modified siRNAs. Nat Biotechnol 23:1002–1007Google Scholar
  85. 85.
    Manoharan M (2004) RNA interference and chemically modified small interfering RNAs. Curr Opin Chem Biol 8:570–579Google Scholar
  86. 86.
    Mouritzen P, Nielsen AT, Pfundheller HM, Choleva Y, Kongsbak L, Moller S (2003) Single nucleotide polymorphism genotyping using locked nucleic acid (LNA). Expert Rev Mol Diagn 3:27–38Google Scholar
  87. 87.
    Crinelli R, Bianchi M, Gentilini L, Magnani M (2002) Design and characterization of decoy oligonucleotides containing locked nucleic acids. Nucleic Acids Res 30(11):2435–2443Google Scholar
  88. 88.
    Monn STM, Schürch S (2007) New aspects of the fragmentation mechanisms of unmodified and methylphosphonate-modified oligonucleotides. J Am Soc Mass Spectrom 18:984–990Google Scholar
  89. 89.
    Huang T-Y, Kharlamova A, McLuckey SA (2010) Ion trap collision-induced dissociation of locked nucleic acids. J Am Soc Mass Spectrom 21:144–153Google Scholar
  90. 90.
    Nyakas A, Stucki SR, Schürch S (2011) Tandem mass spectrometry of modified and platinated oligoribonucleotdes. J Am Soc Mass Spectrom 22:875–887Google Scholar
  91. 91.
    Smith SI, Brodbelt JS (2011) Hybrid activation methods for elucidating nucleic acid modifications. Anal Chem 83:303–310Google Scholar
  92. 92.
    Gao Y, McLuckey SA (2012) Collision-induced dissociation of oligonucleotide anions fully modified at the 2′-position of the ribose: 2′-F/-H and 2′-F/-H/-OMe mix-mers. J Mass Spectrom 47:364–369Google Scholar
  93. 93.
    Gao Y, McLuckey SA (2013) Electron transfer followed by collision-induced dissociation (NET-CID) for generating sequence information from backbone-modified oligonucleotide anions. Rapid Commun Mass Spectrom 27:249–257Google Scholar
  94. 94.
    Baker TR, Keough T, Dobson RLM, Riley TA, Hasselfield JA, Hesselberth PE (1993) Antisense DNA oligonucleotides.1. The use of ionspray tandem mass-spectrometry for the sequence verification of methylphosphonate oligodeoxyribonucleotides. Rapid Commun Mass Spectrom 7:190–194Google Scholar
  95. 95.
    Altmann K, Dean NM, Fabbro D, Freier SM, Geiger T, Häner R, Hüsken D, Martin P, Monia BP, Müller M, Natt F, Nicklin P, Phillips J, Pieles U, Sasmor H, Moser HE (1996) Second generation of antisense oligonucleotides: from nuclease resistance to biological efficacy in animals. Chimia 50:168–176Google Scholar
  96. 96.
    Eckstein F (2000) Phosphorothioate oligonucleotides: what is their origin and what is unique about them? Antisense Nucleic Acids Drug Dev 10:117–121Google Scholar
  97. 97.
    Kurreck J (2003) Antisense technologies: improvement through novel chemical modifications. Eur J Biochem 270:1628–1644Google Scholar
  98. 98.
    Gao Y, Yang J, Cancilla MT, Meng F, McLuckey SA (2013) Top-down interrogation of chemically modified oligonucleotides by negative electron transfer and collision induced dissociation. Anal Chem 85:4713–4720Google Scholar
  99. 99.
    Little DP, Speir JP, Senko MW, O’Connor PB, McLafferty FW (1994) Infrared multiphoton dissociation of large multiply charged ions for biomolecule sequencing. Anal Chem 66:2809–2815Google Scholar
  100. 100.
    Woodin RL, Bomse DS, Beauchamp JL (1978) Multiphoton dissociation of molecules with low power continuous wave infrared laser radiation. J Am Chem Soc 100:3248–3250Google Scholar
  101. 101.
    Håkansson K, Cooper HJ, Hudgins RR, Nilsson CL (2003) High resolution tandem mass spectrometry for structural biochemistry. Curr Org Chem 7:1503–1525Google Scholar
  102. 102.
    Stephenson JL Jr, Booth MM, Shalosky JA, Eyler JR, Yost RA (1994) Infrared multiphoe-photon dissociation in the quadrupole ion trap via a multipass ootical arrangement. J Am Soc Mass Spectrom 5:886–893Google Scholar
  103. 103.
    Hofstadler SA, Sannes-Lowery KA, Griffey RH (1999) Infrared multiphoton dissociation in an external ion reservoir. Anal Chem 71:2067–2070Google Scholar
  104. 104.
    Crowe MC, Brodbelt JS (2005) Differentiation of phosphorylated and unphosphorylated peptides by high-performance liquid chromatography-electrospray ionization-infrared multiphoton dissociation in a quadrupole ion trap. Anal Chem 77:5726–5734Google Scholar
  105. 105.
    Flora JW, Muddiman DC (2001) Selective, sensitive, and rapid phosphopeptide identification in enzymatic digests using ESI-FTICR-MS with infrared multiphoton dissociation. Anal Chem 73:3305–3311Google Scholar
  106. 106.
    Hofstadler SA, Griffey RH, Pasa-Tolic L, Smith RD (1998) The use of a stable internal mass standard for accurate mass measurements of oligonucleotide fragment ions using electrospray ionization fourier transform ion cyclotron resonance mass spectrometry with infrared multiphoton dissociation. Rapid Commun Mass Spectrom 12:1400–1404Google Scholar
  107. 107.
    Sannes-Lowery KA, Hofstadler SA (2003) Sequence confirmation of modified oligonucleotides using IRMPD in the external ion reservoir of an electrospray ionization fourier transform ion cyclotron mass spectrometer. J Am Soc Mass Spectrom 14:825–833Google Scholar
  108. 108.
    Keller KM, Brodbelt JS (2004) Collisionally activated dissociation and infrared multiphoton dissociation of oligonucleotides in a quadrupole ion trap. Anal Biochem 326:200–210Google Scholar
  109. 109.
    Yang J, Håkansson K (2009) Characterization of oligodeoxynucleotide fragmentation pathways in infrared multiphoton dissociation and electron detachment dissociation by Fourier transform ion cyclotron double resonance. Eur J Mass Spectrom 15:293–304Google Scholar
  110. 110.
    Parr C, Brodbelt JS (2010) Increased sequence coverage of thymine-rich oligodeoxynucleotides by infrared multiphoton dissociation compared to collision-induced dissociation. J Mass Spectrom 45:1098–1103Google Scholar
  111. 111.
    Gardner MW, Li N, Ellington AD, Brodbelt JS (2010) Infrared multiphoton dissociaiton of small-interfering RNA anions and cations. J Am Soc Mass Spectrom 21:580–591Google Scholar
  112. 112.
    Comisarow MB, Grassi V, Parisod G (1978) Fourier transform ion cyclotron double resonance. Chem Phys Lett 57:413–416Google Scholar
  113. 113.
    Cooper HJ, Hakansson K, Marshall AG (2005) The role of electron capture dissociation in biomolecular analysis. Mass Spectrom Rev 24:201–222Google Scholar
  114. 114.
    Horn DM, Ge Y, McLafferty FW (2000) Activated ion electron capture dissociation for mass spectral sequencing of larger (42 kDa) proteins. Anal Chem 72:4778–4784Google Scholar
  115. 115.
    Kjeldsen F, Haselmann KF, Budnik BA, Sorensen ES, Zubarev RA (2003) Complete characterization of posttranslational modification sites in the bovine milk protein PP3 by tandem mass spectrometry with electron capture dissociation as the last stage. Anal Chem 75:2355–2361Google Scholar
  116. 116.
    Håkansson K, Hudgins RR, Marshall AG, O’Hair RAJ (2003) Electron capture dissociation and infrared multiphoton dissociation of oligodeoxynucleotide dications. J Am Soc Mass Spectrom 14:23–41Google Scholar
  117. 117.
    Schultz KN, Hakansson K (2004) Rapid electron capture dissociation of mass-selectively accumulated oligodeoxynucleotide dications. Int J Mass Spectrom 234:123–130Google Scholar
  118. 118.
    Yang J, Mo JJ, Adamson JT, Håkansson K (2005) Characterization of oligodeoxynucleotides by electron detachment dissociation Fourier transform ion cyclotron resonance mass spectrometry. Anal Chem 77:1876–1882Google Scholar
  119. 119.
    Huang T-Y, McLuckey SA (2011) Gas-phase ion/ion reactions of rubrene cations and multiply charged DNA and RNA anions. Int J Mass Spectrom 304:140–147Google Scholar
  120. 120.
    Yoo HJ, Wang N, Zhuang SY, Song HT, Håkansson K (2011) Negative-ion electron capture dissociation: radical-driven fragmentation of charge-increased gaseous peptide anions. J Am Chem Soc 133:16790–16793Google Scholar
  121. 121.
    Smith SI, Brodbelt JS (2010) Characterization of oligodeoxynucleotides and modifications by 193 nm photodissociation and electron photodissociation dissociation. Anal Chem 82:7218–7226Google Scholar
  122. 122.
    Gabelica V, TabarIn T, Antolne R, Rosu F, Compagnon I, Broyer M, De Pauw E, Dugourd P (2006) Electron photodetachment dissociation of DNA polyanions in a quadrupole ion trap mass spectrometer. Anal Chem 78:6564–6572Google Scholar
  123. 123.
    Gabelica V, Rosu F, Tabarin T, Kinet C, Antoine R, Broyer M, De Pauw E, Dugourd P (2007) Base-dependent electron photodetachment from negatively charged DNA strands upon 260-nm laser irradiation. J Am Chem Soc 129:4706–4713Google Scholar
  124. 124.
    Guan Z, Kelleher NL, O’Connor PB, Aaserud DJ, Little DP, McLafferty FW (1996) 193 nm Photodissociation of larger multiply charge biomolecules. Int J Mass Spectrom Ion Processes 157/158:357–364Google Scholar
  125. 125.
    Wetmore SD, Boyd RJ, Eriksson LA (2000) Electron affinities and ionization potentials of nucleotide bases. Chem Phys Lett 322:129–135Google Scholar
  126. 126.
    Oberacher H, Pitterl F (2009) On the use of ESI-QqTOF-MS/MS for the comparative sequencing of nucleic acids. Biopolymers 91:401–409Google Scholar
  127. 127.
    Flosadóttir HD, Gíslason K, Sigurdsson ST, Ingólfsson O (2012) Mass spectro-metric study on sodium ion induced central nucleotide deletion in the gas phase. J Am Soc Mass Spectrom 23:690–698Google Scholar
  128. 128.
    Giessing AMB, Kirpekar F (2012) Mass spectrometry in the biology of RNA and its modifications. J Proteomics 75:3434–3449Google Scholar
  129. 129.
    Taucher M, Rieder U, Breuker K (2010) Minimizing base loss and internal fragmentation in collisionally activated dissociation of multiply deprotonated RNA. J Am Soc Mass Spectrom 21:278–285Google Scholar
  130. 130.
    Meng Z, Limbach PA (2005) Shotgun sequencing small oligonucleotides by nozzle-skimmer dissociation and electrospray ionization mass spectrometry. Eur J Mass Spectrom 11:221–229Google Scholar
  131. 131.
    Taucher M, Breuker K (2010) Top-down mass spectrometry for sequencing of larger (up to 61 nt) RNA by CAD and EDD. J Am Soc Mass Spectrom 21:918–929Google Scholar
  132. 132.
    Taucher M, Breuker K (2012) Characterization of modified RNA by top-down mass spectrometry. Angew Chem 124:11451–11454Google Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  1. 1.Department of ChemistryPurdue UniversityWest LafayetteUSA

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