Location of the Negative Charge(s) on the Backbone of Single-Stranded Deoxyribonucleic Acid in the Gas Phase

Favre, Amélie; Gonnet, Florence; Tabet, Jean‐Claude

doi:10.1255/ejms.360

Cited by 19 publications

(32 citation statements)

References 21 publications

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“…The fact that w 5 Ϫ2 and w 6 Ϫ2 species were not observed suggests that in the activated parent species, the total charge was not distributed statistically along the phosphate backbone, but was instead confined near the 5=-and 3=-termini. Analysis of the a-B ion series in Figure 2a supports the same conclusion, which is also consistent with results for different sequences in previous studies [35].…”

Section: Fragmentation Of Low Charge State Precursorssupporting

confidence: 91%

“…The assortment of sequence ions visible in Figure 2a indicates that cleavage has occurred at nearly every interresidue junction along the phosphate backbone, as indicated by the series of slash marks overlaid on the sequence shown in Figure 2a. As originally described by Favre et al [35], the charges on these sequence ions convey the preferred locations of the negative charges. For example, the w ion series in Figure 2a consisted of w 2 Ϫ1 , w 5 Ϫ1 , w 6 Ϫ1 , w 8 Ϫ2 , and w 9 Ϫ2 species.…”

Section: Fragmentation Of Low Charge State Precursorsmentioning

confidence: 88%

“…Favre et al observed a number of a n Ϫm ions upon collisional activation of deprotonated polythymine, a result that was ascribed to the low proton affinity of thymine [35]. The formation of a n Ϫm ions has also been observed as highly diagnostic for the modification sites of photomodified ODNs in which two nucleobases are covalently bonded.…”

Section: Sequencementioning

confidence: 99%

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Charge state-dependent fragmentation of oligonucleotide/metal complexes

Keller

Brodbelt

2005

J. Am. Soc. Mass Spectrom.

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Collision-activated dissociation (CAD) has been employed to assess the gas-phase fragmentation behavior of a series of 1:1 oligodeoxynucleotide (ODN):metal complexes over a range of charge states, using several ten-residue ODNs and a wide array of alkali, alkaline earth, and transition metals. For parent species in low to intermediate charge states, complexation with Ca ϩ2 , Sr ϩ2 , or Ba ϩ2 altered the relative intensity of M-B species, promoting loss of cytosine over loss of guanine. The relative intensities of sequence ions were largely unaffected. This behavior was most prevalent for isomeric sequences with complementary residues at the 5=-and 3=-termini, suggesting that metal complexation may change the gas-phase conformation and/or conformational dynamics for some sequences. In higher charge states, some ODN/ Ba ϩ2 complexes produced abundant fragment ions corresponding to metallated a n Ϫm species, which are not commonly observed in CAD mass spectra for deprotonated ODNs. The formation of these ions was most favored for complexes between Ba ϩ2 and ODN sequences with a thymine residue at Position 6. Literature precedent exists for the formation of a n Ϫm ions from sequences in which covalent modification generates one or more neutral sites along the phosphate backbone. ODN/metal adducts in high charge states possess only a few acidic protons, and the juxtaposition of these neutral phosphate groups near thymine residues and the bound Ba ϩ2 ion may direct formation of the metallated a n Ϫm species. and function of DNA and RNA. Mono-and divalent cations are thought to induce bending in DNA duplexes [1,2], and are also known to stabilize triplex [3,4], and quadruplex [5,6] structures. Metal cations are also required for the proper folding and function of many forms of RNA, including most ribozymes [7,8]. The interactions of DNA with several natural products [9] and synthetic drugs and drug candidates [10,11] are known to be metal-mediated.Mass spectrometry (MS) is well-established as a useful tool for the structural characterization and sequencing of nucleic acids [12][13][14], and has also been employed to characterize a number of nucleic acid/metal ion interactions [15]. Several previous studies have focused on the interactions of the anticancer therapeutic cisplatin or its derivatives with DNA [16 -22]. Relatively few studies have addressed binary interactions of nucleic acids and metal cations [23][24][25][26][27]. Most of these studies have focused primarily on complexes with the smaller alkali and alkaline earth metals (e.g., Na ϩ , Mg ϩ2 ), although a few complexes with transition metals [25,26] or f-block elements [23,25] have also been investigated. The fragmentation behavior of these complexes has been characterized using parent species in relatively low charge states (often Ϫ2), but intermediate and high charge state precursors have not been studied. A more complete characterization of the entire charge state envelope produced by electrospray ionization would not only enhance our theoretical underst...

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Section: Fragmentation Of Low Charge State Precursorssupporting

confidence: 91%

Section: Fragmentation Of Low Charge State Precursorsmentioning

confidence: 88%

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Charge state-dependent fragmentation of oligonucleotide/metal complexes

Keller

Brodbelt

2005

J. Am. Soc. Mass Spectrom.

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“…The dissociation of deprotonated ODNs has been extensively investigated by mass spectrometry (MS) coupled with soft ionization methods such as electrospray (ESI) and matrix-assisted laser desorption ionization (MALDI) [1][2][3][4][5][6][7][8][9][10][11][12][13][14]. It is known that the first step in the dissociation of deprotonated ODNs is loss of a nucleobase, either in a neutral (BH) or deprotonated (B Ϫ ) form [1,2,15].…”

mentioning

confidence: 99%

“…The loss of a nucleobase as a deprotonated anion or as a neutral is dependent on the identity of the base and the charge state of the parent ODN ion [2,4,8,16]. The higher charge states favor B Ϫ loss while lower charge states favor BH loss.…”

mentioning

confidence: 99%

Investigation of the initial fragmentation of oligodeoxynucleotides in a quadrupole ion trap: Charge level-related base loss

Pan

Verhoeven

Lee

2005

J. Am. Soc. Mass Spectrom.

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The charge state distribution and CID fragmentation of two series of deprotonated oligodeoxynucleotide (ODN) 9-mers (5=-GGTTXTTGG-3= and 5=-CCAAYAACC-3=, X/Y ϭ G, C, A, or T) have been studied in detail in an ion trap in an effort to understand the intrinsic properties of DNA in vacuo. The distribution of charge states (Ϫ2 to Ϫ6) is similar for both the X-and Y-series, with the most abundant being the Ϫ4 charge state. The T-rich X-series prefers higher charge states (Ϫ6 and Ϫ5) than does the Y-series. Calculations show that phosphate groups located nearest a thymine are more acidic than those near an adenine, cytosine, or guanine, thus explaining why the X-series prefers higher charge states. We use the term "charge level" to define the ratio of the charge state to the total number of phosphate groups present in the ODN. We find, consistent with previous studies, that the initial step of fragmentation is loss of nucleobase either as an anion or as a neutral. We observe the former for ODNs with charge levels greater than 50% and the latter for ODNs with charge levels below 50%. The overall anionic base loss follows the trend A Ϫ Ͼ Ͼ G Ϫ Ϸ T Ϫ Ͼ C Ϫ ; electrostatic potential calculations indicate that this trend follows delocalization of electron density for each anion, with A Ϫ being the most stabilized through delocalization. For neutral base loss, thymine (TH) is rarely cleaved, while the preferences for AH, GH, and CH loss vary. Proton affinity (PA) calculations show that a nearby negatively charged phosphate enhances the PA of proximally located nucleobases; this PA enhancement probably plays a role in promoting neutral base loss. The trends differ by charge level. At a charge level of 37.5% (Ϫ3 charge state), AH loss is preferred over CH and GH loss, regardless of sequence. However, at a charge level of 25% (Ϫ2 charge state), the terminal bases are preferentially lost over the internal bases, regardless of identity. By reconstructing the ODN sequences from structurally informative (a-BH) and w ions, we are able to identify the charge locations for the Ϫ3 and Ϫ2 charge states. For the Ϫ3 charge state, one charge resides on each "most terminal" phosphate, with the third being in the middle. For the Ϫ2 charge state, each charge resides on the penultimate phosphate groups. We compare our data to earlier experiments in an effort to generalize trends. (J Am Soc Mass Spectrom 2005, 16, 1853-1865

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Charge State Distributions in Electrospray and MALDI

Cole

2010

Electrospray and MALDI Mass Spectrometry

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Location of the Negative Charge(s) on the Backbone of Single-Stranded Deoxyribonucleic Acid in the Gas Phase

Cited by 19 publications

References 21 publications

Charge state-dependent fragmentation of oligonucleotide/metal complexes

Charge state-dependent fragmentation of oligonucleotide/metal complexes

Investigation of the initial fragmentation of oligodeoxynucleotides in a quadrupole ion trap: Charge level-related base loss

Charge State Distributions in Electrospray and MALDI

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