Combined strategies for suppressing nonspecific cationic adduction to G-quadruplexes in electrospray ionization mass spectrometry

Wen, Lei; Hu, Jun; Chen, Hong‐Yuan; Xu, Jing‐Juan

doi:10.1016/j.aca.2022.340146

Cited by 2 publications

(6 citation statements)

References 37 publications

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“…It maybe wondered how G4 ions free of non-specific adduction are produced by simply employing a nanopore ion emitter. Baker, Williams, Donald, our group, , and others have previously proposed that the suppression of non-specific adduction should be attributed to the small initial droplets when using a nanoscale ion emitter. The sizes of the initial droplets are approximately 1/10–1/17 of the emitter diameter in conventional electrospraying. − If this can be extended to the nanoscale region, the sizes of initial droplets are thus expected to be only 2–3 nm when a 30 nm emitter is used, which is close to the sizes of G4s in this work (∼3 nm) .…”

Section: Resultsmentioning

confidence: 89%

“…It maybe wondered how G4 ions free of non-specific adduction are produced by simply employing a nanopore ion emitter. Baker, 32 Williams, 26 Donald, 25 our group, 24,28 and others have previously proposed that the suppression of nonspecific adduction should be attributed to the small initial droplets when using a nanoscale ion emitter. The sizes of the initial droplets are approximately 1/10−1/17 of the emitter diameter in conventional electrospraying.…”

Section: ■ Results and Discussionmentioning

confidence: 93%

“…Similar to that of the K + buffers, mass spectrum obtained from buffer containing 10 mM Tris-HCl/140 mM NaCl was also not interfered by salt clusters when a nanopore emitter was used (see Figure 1h). It is worth noting that the coordination of Na + in G4s is typically much weaker than that of K + (about 2 orders of magnitude lower for 24TTG in terms of their dissociation constants) 28 and it thus require much higher Na + concentration to form G4-Na + complexes. This might be the reason why MS of G-quadruplexes containing sodium was rarely reported.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

“…We ascribe this phenomenon to the ultrasmall droplets, high surface charge-to-volume ratio, and high electric field according to the previous nanopore ion emitter literatures. 28,32 Additionally, G4s tend to carry more charges due to their intrinsic property (carrying a lot of ionizable phosphate groups), compared with proteins which nanopore ion emitters often detect. Benefiting from the nearly total suppression of both non-specific cationic adducts and salt clusters, the accurate stoichiometry of specifically bound cations (e.g., Na + and K + ) or ligands (e.g., PaH) in various G4s (e.g., antiparallel, parallel and hybrid topologies) can be directly obtained from the clean mass spectra without interference.…”

Section: ■ Conclusionmentioning

confidence: 99%

“…Despite the massive non-specific cationic adduction, such submicrometer ion emitters also exhibited improved tolerance of the non-volatile salts (up to 40 mM) for the detection of nucleic acids . We recently demonstrated a combined strategy that takes full advantages of a small ion emitter and partial TMAA replacement to suppress non-specific Na + /K + adduction, which permitted measuring the specific coordination of Na + /K + in G4s from solutions containing up to 25 mM NaCl/KCl . Nevertheless, the ultimate goal in achieving MS analysis of G4s directly from their native biochemical buffers has never been accomplished.…”

Section: Introductionmentioning

confidence: 99%

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Nanopore Liberates G-Quadruplexes from Biochemical Buffers for Accurate Mass Spectrometric Examination

Wen

Chen

et al. 2022

Anal. Chem.

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Achieving accurate measurements of G-quadruplexes (G4s), especially the characterization of their complicated non-covalent interactions with various components (such as metal ions and ligands) under physiological conditions, is of fundamental significance in unveiling their biological roles and developing antitumor drugs. By employing a nanopore ion emitter (∼30 nm), we demonstrated for the first time that G4 ions, which are free of non-specific adduction and meanwhile maintaining their pre-existing specific bindings with metal ions or ligands, can be directly liberated from common biochemical buffers (consisting of concentrated non-volatile salts of >150 mM) for mass spectrometric examination. Notably, the intermediate complexes of G4s with mixed di-cation coordination formed during the Na + /K + exchange were successfully observed by mass spectrometry, whose structures were also revealed by the reconstructed circular dichroism spectra. We believe the nanopore-based ion emitters have built a solid bridge between native G4s in aqueous buffers and their accurate stoichiometries obtained by mass spectrometric examination.

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Section: Resultsmentioning

confidence: 89%

Section: ■ Results and Discussionmentioning

confidence: 93%

Section: ■ Results and Discussionmentioning

confidence: 99%

Section: ■ Conclusionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Nanopore Liberates G-Quadruplexes from Biochemical Buffers for Accurate Mass Spectrometric Examination

Wen

Chen

et al. 2022

Anal. Chem.

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Lighting Up at High Potential: Effects of Voltage and Emitter Size in Nanoelectrospray Ionization

Jordan

Miller

Harper

et al. 2023

J. Am. Soc. Mass Spectrom.

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Effects of electrospray voltage on cluster size and abundance formed from aqueous CsI were investigated with emitter tip diameters between 260 ± 7 nm and 2.45 ± 0.30 μm. Cluster size increases with increasing voltage, increasing solution concentration and increasing emitter diameter consistent with formation of larger initial droplet sizes. For emitters with tip diameters above ∼1 μm, varying the voltage either up or down leads to reproducible voltage-dependent extents of cluster formation. In contrast, higher voltages with submicron diameter emitters can lead to only Cs+ and Cs(H2O)+ and no clusters. This change in ion formation reproducibly occurs at spray potentials >1.3 kV for 260 nm emitters and appears to be induced by a corona discharge and material build-up at the emitter tip. Under conditions where abundant Cs+ is observed and no clusters are formed, ions such as K+ and Cu1+ are also observed but ions with more negative solvation energies, such as Ba2+, are not. Similarly, ions from bradykinin and ubiquitin are observed predischarge but not post discharge. Ions with more positive solvation energies can desorb directly from the air–water interface that is created at the tip of these emitters, whereas ions with more negative solvation energies as well as peptide and protein ions do not. These results indicate that ion desorption directly from solution can occur, and similar experiments with even smaller emitters may lead to new insights into ion formation in electrospray ionization.

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Combined strategies for suppressing nonspecific cationic adduction to G-quadruplexes in electrospray ionization mass spectrometry

Cited by 2 publications

References 37 publications

Nanopore Liberates G-Quadruplexes from Biochemical Buffers for Accurate Mass Spectrometric Examination

Nanopore Liberates G-Quadruplexes from Biochemical Buffers for Accurate Mass Spectrometric Examination

Lighting Up at High Potential: Effects of Voltage and Emitter Size in Nanoelectrospray Ionization

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