Electrospray mass spectrometry to study drug-nucleic acids interactions

Rosu, Frédéric; Pauw, Edwin De; Gabelica, Valérie

doi:10.1016/j.biochi.2008.01.005

Cited by 163 publications

(264 citation statements)

References 99 publications

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“…3 Electrospray ionization mass spectrometry (ESI-MS) in native conditions helps deciphering the complexation equilibria. [4][5][6][7] Coupled to ion mobility spectrometry (IMS), native mass spectrometry makes it possible to reveal the ensuing conformational responses. [8][9][10] But before native ESI-IMS-MS can be applied to study nucleic acids conformations from solution, it is essential to understand to what extent the different types of DNA/RNA secondary structures are preserved, or affected, by the transition from the solution to the gas phase.…”

Section: Introductionmentioning

confidence: 99%

Compaction of Duplex Nucleic Acids upon Native Electrospray Mass Spectrometry

Porrini

Rosu

Rabin

et al. 2017

Preprint

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ABSTRACT:Native mass spectrometry coupled to ion mobility spectrometry is a promising tool for structural biology. Intact complexes can be transferred to the mass spectrometer and, if native conformations survive, collision cross sections give precious information on the structure of each species in solution. Based on several successful reports for proteins and their complexes, the conformation survival becomes more and more taken for granted. Here we report on the fate of nucleic acids conformation in the gas phase. Disturbingly, we found that DNA and RNA duplexes, at the electrospray charge states naturally obtained from native solution conditions (≥ 100 mM aqueous NH 4 OAc), are significantly more compact in the gas phase compared to the canonical solution structures. The compaction is observed for short (12-bp) and long (36-bp) duplexes, and for DNA and RNA alike. Molecular modeling (density functional calculations on small helices, semi-empirical calculations on up to 12-bp, and molecular dynamics on up to 36-bp duplexes) demonstrates that the compaction is due to phosphate group self-solvation prevailing over Coulomb-driven expansion. Molecular dynamics simulations starting from solution structures do not reproduce the experimental compaction. To be experimentally relevant, molecular dynamics sampling should reflect the progressive structural rearrangements occurring during desolvation. For nucleic acid duplexes, the compaction observed for low charge states results from novel phosphate-phosphate hydrogen bonds formed across both grooves at the very late stages of electrospray.

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Section: Introductionmentioning

confidence: 99%

Compaction of Duplex Nucleic Acids upon Native Electrospray Mass Spectrometry

Porrini

Rosu

Rabin

et al. 2017

Preprint

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“…Ammonium ions allow salt adducts to be avoided because complete solvent evaporation is followed by proton transfer between NH 4 + and PO ! from the negatively charged phosphodiester backbone, and in consequence ions that are not coordinated between G-tetrads evaporate as NH 3 (Gabelica, 2010;Rosu et al, 2008). Usually the detected number of ammonium ions is one less than the number of G-tetrad planes involved in the structure formation, as only one ion is typically found between each pair of adjacent G-tetrads.…”

Section: Electrospray Ionization Mass Spectrometry (Esi-ms)mentioning

confidence: 99%

How to study G-quadruplex structures

Małgowska¹,

Gudanis²,

Teubert³

et al. 2012

bta

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All guanine-rich DNA and RNA molecules tend to fold into inter-and intra-molecular structures called G-quadruplexes. The core of a G-quadruplex is composed of at least two adjacent G-tetrads stabilized by monovalent cations. While it has been suggested that there could potentially be over 375 000 quadruplex forming sequences in the human genome alone, only a small number of three-dimensional G-quadruplex structures are known. More structural data are needed to explain their presence and function in vivo. We offer here a short review of experimental methods commonly used to determine G-quadruplex topologies.

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“…Furthermore, if the evaporation and transfer steps are conducted in soft conditions, intact noncovalently bound DNA structures like duplexes, 43,44 quadruplexes, 39,[44][45][46][47][48] and PNA•DNA assemblies [49][50][51][52] can be preserved from the solution and detected in the mass spectrometer. Three review articles [53][54][55] describing various application of mass spectrometry for the study of nucleic acid non-covalent complexes by ESI-MS can be consulted for more references.…”

Section: Introductionmentioning

confidence: 99%

Hybridization of short complementary PNAs to G‐quadruplex forming oligonucleotides: An electrospray mass spectrometry study

et al. 2008

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We investigated the interaction of the short PNA strand [acccca]-PNA with oligodeoxynucleotides containing one, two, or four tracts of TGGGGT units. Electrospray ionization mass spectrometry allowed exploring the wide variety of complex stoichiometries that were found to coexist in solution. In water, the PNA strand forms short heteroduplexes with the complementary DNA sequences, but higher-order structures are also found, with PNA 2n •DNA n triplex units, culminating in precipitation at very low ionic strength. In the presence of ammonium acetate, there is a competition between PNA•DNA heteroduplex formation and DNA G-quadruplex formation. Heteroduplex formation is favored when the PNA + DNA mixture in ammonium acetate is heated and cooled at room temperature, but not if the PNA is added at room temperature to the pre-formed G-quadruplex. We also found that the short [acccca]-PNA strand binds to G-quadruplexes.

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Electrospray mass spectrometry to study drug-nucleic acids interactions

Cited by 163 publications

References 99 publications

Compaction of Duplex Nucleic Acids upon Native Electrospray Mass Spectrometry

Compaction of Duplex Nucleic Acids upon Native Electrospray Mass Spectrometry

How to study G-quadruplex structures

Hybridization of short complementary PNAs to G‐quadruplex forming oligonucleotides: An electrospray mass spectrometry study

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