Stability of complementary and mismatched DNA duplexes: Comparison and contrast in gas versus solution phases

Pan, Su‐Shu; Sun, Xuejun; Lee, Jeehiun K.

doi:10.1016/j.ijms.2006.03.014

Cited by 31 publications

(55 citation statements)

References 78 publications

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“…In each spectrum, consistent with others' results, both single strands and duplexes are detected [12,32,39,40,42]. The presence of the single strands could be attributable to disruption of the duplex by the ESI process, and/or the presence of single strands in solution which then get electrosprayed and appear in the spectra; probably it is a combination of both factors (vide infra) [19].…”

Section: Full-scan Mass Spectrometry Of Dna Duplexessupporting

confidence: 87%

“…Experimental conditions were tuned by optimizing the Ϫ3 charged duplex ions of 8-mer-II (m/z ϭ 1605); the parameters thus obtained were applied to all the duplexes except those containing O 6 -methylguanine. The four 9-mer duplexes containing O 6 -methylguanine were examined under slightly different tuning conditions, which have been described previously [19].…”

Section: Esi-quadrupole Ion Trap Mass Spectrometermentioning

confidence: 99%

“…The average standard deviation of the E 50 values is Ϯ0.06. It should also be noted that while absolute E 50 s, like T m s, can change under different experimental conditions, a series studied under the same conditions should have relatively comparable E 50 values [19,35].…”

Section: Esi-quadrupole Ion Trap Mass Spectrometermentioning

confidence: 99%

“…The characterization of duplex stability in the gas phase can be accomplished by a variety of methods; one relatively straightforward technique is CID in an ion trap mass spectrometer [10 -18]. In previous work, we focused on the behavior of a series of 9-mer complementary and mismatched DNA duplexes at the Ϫ4 charge state [19]. In the present work, we wish to further expand our understanding of gas-phase DNA behavior by examining a systematic series of duplexes that differ in sequence, length, and charge state.…”

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confidence: 99%

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DNA stability in the gas versus solution phases: A systematic study of thirty-one duplexes with varying length, sequence, and charge level

Pan

Sun

Lee

2006

J. Am. Soc. Mass Spectrom.

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We report herein a systematic mass spectrometric study of a series of thirty-one non-selfcomplementary, matched, DNA duplexes ranging in size from 5-to 12-mers. The purpose of this work is threefold: (1) to establish the viability of using mass spectrometry as a tool for examining solution phase stabilities of DNA duplexes; (2) to systematically assess gas-phase stabilities of DNA duplexes; and (3) to compare gas and solution phase stabilities in an effort to understand how media affects DNA stability. These fundamental issues are of importance both on their own, and also for harnessing the potential of mass spectrometry for biological applications. We have found that ion abundances do not always track with solution phase stability; GC content must be taken into account. Two duplexes with the same T m yet with differing GC content can yield different ion abundances. That is, if two duplexes have the exact same melting temperature, yet one has a higher GC content, the duplex with the higher GC content yields a higher ion abundance. It thus appears that not only is a GC base pair stronger than an AT base pair, but the relative strengths of each differ in the gas phase versus in solution, such that the electrospray process can differentiate between them. We also characterize the gas-phase stabilities of the duplexes, using collision-induced dissociation (CID) as a method to assess stability. We focus on two aspects of this CID experiment. One, we examine what factors appear to control whether the duplexes dissociate into single strands or covalently fragment; we are able to utilize a charge state normalization we coin "charge level" to compare our results with others' and establish generalities regarding dissociation versus fragmentation patterns. Two, we examine those duplexes that primarily dissociate and use CID to assess the gas-phase stabilities. We find that correlation of gas-phase to solution-phase stabilities is more likely to occur when duplexes of varying GC content are examined. Duplexes with the same GC content tend to have stabilities that do not parallel those in solution. We discuss these results in light of the different roles that hydrogen bonding and base stacking play in solution versus the gas phase. Ultimately, we apply what we learn to lend insight into the biological problem of how the carcinogenic, damaged nucleobase O 6 -methylguanine causes mutations. (J Am Soc Mass Spectrom 2006, 17, 1383-1395

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Section: Full-scan Mass Spectrometry Of Dna Duplexessupporting

confidence: 87%

Section: Esi-quadrupole Ion Trap Mass Spectrometermentioning

confidence: 99%

Section: Esi-quadrupole Ion Trap Mass Spectrometermentioning

confidence: 99%

mentioning

confidence: 99%

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DNA stability in the gas versus solution phases: A systematic study of thirty-one duplexes with varying length, sequence, and charge level

Pan

Sun

Lee

2006

J. Am. Soc. Mass Spectrom.

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“…The relative signal intensities of matched and mismatched duplexes correlate well with the in-solution stability of the duplex [16]. Alternatively, the stability of a duplex can be evaluated with the E 50 value, which corresponds to the activation energy required to dissociate 50% of the duplex.…”

Section: Ms/ms Of Dna Duplexesmentioning

confidence: 99%

The Contribution of the Activation Entropy to the Gas-Phase Stability of Modified Nucleic Acid Duplexes

Hari

Dugovic

Istrate

et al. 2016

J. Am. Soc. Mass Spectrom.

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Abstract. Tricyclo-DNA (tcDNA) is a sugar-modified analogue of DNA currently tested for the treatment of Duchenne muscular dystrophy in an antisense approach. Tandem mass spectrometry plays a key role in modern medical diagnostics and has become a widespread technique for the structure elucidation and quantification of antisense oligonucleotides. Herein, mechanistic aspects of the fragmentation of tcDNA are discussed, which lay the basis for reliable sequencing and quantification of the antisense oligonucleotide. Excellent selectivity of tcDNA for complementary RNA is demonstrated in direct competition experiments. Moreover, the kinetic stability and fragmentation pattern of matched and mismatched tcDNA heteroduplexes were investigated and compared with non-modified DNA and RNA duplexes. Although the separation of the constituting strands is the entropy-favored fragmentation pathway of all nucleic acid duplexes, it was found to be only a minor pathway of tcDNA duplexes. The modified hybrid duplexes preferentially undergo neutral base loss and backbone cleavage. This difference is due to the low activation entropy for the strand dissociation of modified duplexes that arises from the conformational constraint of the tc-sugar-moiety. The low activation entropy results in a relatively high free activation enthalpy for the dissociation comparable to the free activation enthalpy of the alternative reaction pathway, the release of a nucleobase. The gas-phase behavior of tcDNA duplexes illustrates the impact of the activation entropy on the fragmentation kinetics and suggests that tandem mass spectrometric experiments are not suited to determine the relative stability of different types of nucleic acid duplexes.

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Gas‐Phase Chemistry of Organocopper Compounds

Lamsabhi¹,

Yáñez²,

Salpin³

et al. 2011

Patai's Chemistry of Functional Groups

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Introduction Performance of Different Theoretical Models Ligand‐Field Spectroscopy and Photofragmentation Processes Cu + and Cu 2+ Binding Energies Coordination Bonding Cu + / Cu 2+ Reactions with Small Organic Bases Gas‐Phase Reactivity of Copper( I ) and Copper( II ) Ions toward Molecules of Biological Relevance

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Stability of complementary and mismatched DNA duplexes: Comparison and contrast in gas versus solution phases

Cited by 31 publications

References 78 publications

DNA stability in the gas versus solution phases: A systematic study of thirty-one duplexes with varying length, sequence, and charge level

DNA stability in the gas versus solution phases: A systematic study of thirty-one duplexes with varying length, sequence, and charge level

The Contribution of the Activation Entropy to the Gas-Phase Stability of Modified Nucleic Acid Duplexes

Gas‐Phase Chemistry of Organocopper Compounds

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