Thermodynamic and kinetic characterization of the dissociation and assembly of quadruplex nucleic acids

Hardin, Charles C.; Perry, Adam; White, Katie

doi:10.1002/1097-0282(2000/2001)56:3<147::aid-bip10011>3.0.co;2-n

Cited by 234 publications

(188 citation statements)

References 64 publications

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“…To confirm the assignment of m/z 965.5, an MS 3 experiment was performed, and the resulting spectrum ( Figure 7) ion also dissociated by direct backbone cleavage. Some products of cleavage preceded by base loss (likely by the mechanism shown in Scheme 2) are also visible (e.g., *[a 6 -T] Ϫ2 ) in Figure 7.…”

Section: Fragmentation Of High Charge State Precursorsmentioning

confidence: 99%

“…Likewise, comparing data for Ba ϩ2 and K ϩ , which have similar ionic radii (149 versus 152 pm) but different net charges, indicates that greater ionic charge also facilitates formation of the *a 6 Ϫ2 product ion (Figure 6b versus d). Results for other metal ions suggests that other factors are probably also operative: for example, the complex with Pb ϩ2 gave the *a 6 Ϫ2 ion in somewhat lower intensity than the complex with Sr ϩ2 , which could be due to a difference in electronegativity (0.95 for Pb ϩ2 versus 1.87 for Sr ϩ2 ), orbital configuration (two versus zero valence electrons), or both.…”

Section: Fragmentation Of High Charge State Precursorsmentioning

confidence: 99%

“…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].…”

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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 High Charge State Precursorsmentioning

confidence: 99%

Section: Fragmentation Of High Charge State Precursorsmentioning

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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“…Moreover, RNA G-quadruplexes are restricted to adopting a parallel configuration caused by the stronger preference for an anticonformation of the glycosidic bond between the ribose and guanine moieties (Halder and Hartig 2011). Considerable effort has been spent trying to understand the principles which govern the folding of G-quadruplexes (Hardin et al 2000;Xue et al 2011;Karsisiotis et al 2013). Numerous articles have explored the contributions of the composition and length of the loops on the formation and topology of both DNA and RNA G-quadruplexes (Hazel et al 2004;Risitano and Fox 2004;Rachwal et al 2007;Guedin et al 2009Guedin et al , 2010Olsen et al 2009;Zhang et al 2011;Koirala et al 2013;Kwok et al 2013;Pandey et al 2013), and some general conclusions regarding the loops have emerged.…”

Section: Introductionmentioning

confidence: 99%

The folding of 5′-UTR human G-quadruplexes possessing a long central loop

Jodoin

Bauer

Garant

et al. 2014

RNA

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G-quadruplexes are widespread four-stranded structures that are adopted by G-rich regions of both DNA and RNA and are involved in essential biological processes such as mRNA translation. They are formed by the stacking of two or more G-quartets that are linked together by three loops. Although the maximal loop length is usually fixed to 7 nt in most G-quadruplexpredicting software, it has already been demonstrated that artificial DNA G-quadruplexes containing two distal loops that are limited to 1 nt each and a central loop up to 30 nt long are likely to form in vitro. This report demonstrates that such structures possessing a long central loop are actually found in the 5 ′ -UTRs of human mRNAs. Firstly, 1453 potential G-quadruplex-forming sequences (PG4s) were identified through a bioinformatic survey that searched for sequences respecting the requirement for two 1-nt long distal loops and a long central loop of 2-90 nt in length. Secondly, in vitro in-line probing experiments confirmed and characterized the folding of eight candidates possessing central loops of 10-70 nt long. Finally, the biological effect of several G-quadruplexes with a long central loop on mRNA expression was studied in cellulo using a luciferase gene reporter assay. Clearly, the actual definition of G-quadruplex-forming sequences is too conservative and must be expanded to include the long central loop. This greatly expands the number of expected PG4s in the transcriptome. Consideration of these new candidates might aid in elucidating the potentially important biological implications of the G-quadruplex structure.

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“…The monovalent cations stabilize the quadruplex in the order: K + > Rb + > Na + > Cs + > Li + . Divalent cations bind to quadruplexes with higher constants of association (K A ) and the following order in stabilization was observed: Sr 2+ > Ba 2+ > Ca 2+ > Mg 2+ (Hardin et al 2000;Tucker et al 2012). However, the localization of ions in the quadruplex and the stoichiometry of binding are not yet fully clear and, in certain cases, controversial results have been reported.…”

Section: Stability Of Guanine Quadruplexes In Dna Aptamers At Presencmentioning

confidence: 99%

Potential uses of G-quadruplex-forming aptamers

Víglaský

Hianik

2013

gpb

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Abstract. Guanine quadruplex (G-quadruplex) structures are one of a number of structures which are capable of adopting aptamers. G-rich DNA or RNA has an increased propensity to form quadruplex structures which have unusual biophysical and biological properties. G-rich aptamers which form G-quadruplexes have several advantages over unstructured sequences: G-quadruplexes are non-immunogenic, thermodynamically and chemically stable and they have both higher resistance to various serum nucleases and an enhanced cellular uptake. These advantages have led to a number of synthetic oligonucleotides being studied for their potential use as therapeutic agents for cancer therapy and in the treatment of various other diseases. In addition to their suitability in the fields of medicine and biotechnology, these, highly specified, aptameric G-quadruplexes also have great potential in the further development of nano-devices; e.g. basic components in microarrays, microfluidics, sandwich assays and electrochemical biosensors. This review summarizes the biophysical properties of G-quadruplexes and highlights the importance of the stability and recognition properties of aptamers. Examples of the application of aptamers in medical therapy and in biosensors are also discussed.

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Thermodynamic and kinetic characterization of the dissociation and assembly of quadruplex nucleic acids

Cited by 234 publications

References 64 publications

Charge state-dependent fragmentation of oligonucleotide/metal complexes

Charge state-dependent fragmentation of oligonucleotide/metal complexes

The folding of 5′-UTR human G-quadruplexes possessing a long central loop

Potential uses of G-quadruplex-forming aptamers

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