Charge state-dependent fragmentation of oligonucleotide/metal complexes

Abstract

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...

Direct Evidence for Tautomerization of the Uracil Moiety within the Pb2+/Uridine-5′-monophosphate Complex: A Combined Tandem Mass Spectrometry and IRMPD study

“…While the interaction of metal complexes with nucleotides is one of the central topics in bioinorganic chemistry, studies about the gas-phase behavior of such interactions are rather scarce [15][16][17][18][19][20][21][22][23][24][25][26][27][28][29] compared to the numerous papers devoted to the interactions with peptides and proteins. A good knowledge of mechanisms at the molecular level is still lacking in most cases, and to the best of our knowledge, the gas-phase Pb 2+ /nucleotides interactions have not been explored so far.…”

Sodium controlled selective reactivity of protonated deoxy-oligonucleotides in the gas phase

“…The base then leaves the oligonucleotide either protonated or as the neutral base, and the base loss is followed by a backbone cleavage. Studies have also been conducted on the fragmentation of oligonucleotides with a single metal ion attached [27][28][29][30][31][32][33], and Wang et al [34,35] …”

ESI‐MS studies of the non‐covalent interactions between biologically important metal ions and N‐sulfonylcytosine derivatives

“…[16][17][18][19][20] Such interactions have important roles in many biochemical processes in cells. [21] Numerous authors have reported that the ESI-MS technique is a major tool in structure elucidation studies of nucleobase derivatives. [22][23][24] In this study, we elaborate on 1, the stability of ligands N-1-(p-toluenesulfonyl)cytosine, (1-TsC) 1, N-1-(methanesulfonyl) cytosine, (1-MsC) 2, their complexes Cu(1-TsC-N3) 2 Cl 2 3 and Cu(1-MsC-N3) 2 Cl 2 4 ( Fig.…”