Examining DNA Structures with In-droplet Hydrogen/Deuterium Exchange Mass Spectrometry.

Autor: Attanayake K; C. Eugene Bennett Department of Chemistry, West Virginia University, Morgantown, WV, USA., Mahmud S; C. Eugene Bennett Department of Chemistry, West Virginia University, Morgantown, WV, USA., Banerjee C; C. Eugene Bennett Department of Chemistry, West Virginia University, Morgantown, WV, USA., Sharif D; C. Eugene Bennett Department of Chemistry, West Virginia University, Morgantown, WV, USA., Rahman M; C. Eugene Bennett Department of Chemistry, West Virginia University, Morgantown, WV, USA., Majuta S; C. Eugene Bennett Department of Chemistry, West Virginia University, Morgantown, WV, USA., DeBastiani A; C. Eugene Bennett Department of Chemistry, West Virginia University, Morgantown, WV, USA., Sultana MN; C. Eugene Bennett Department of Chemistry, West Virginia University, Morgantown, WV, USA., Foroushani SH; C. Eugene Bennett Department of Chemistry, West Virginia University, Morgantown, WV, USA., Li C; C. Eugene Bennett Department of Chemistry, West Virginia University, Morgantown, WV, USA., Li P; C. Eugene Bennett Department of Chemistry, West Virginia University, Morgantown, WV, USA., Valentine SJ; C. Eugene Bennett Department of Chemistry, West Virginia University, Morgantown, WV, USA.
Jazyk: angličtina
Zdroj: International journal of mass spectrometry [Int J Mass Spectrom] 2024 May; Vol. 499. Date of Electronic Publication: 2024 Mar 07.
DOI: 10.1016/j.ijms.2024.117231
Abstrakt: Capillary vibrating sharp-edge spray ionization (cVSSI) combined with hydrogen/deuterium exchange-mass spectrometry (HDX-MS) has been utilized to characterize different solution-phase DNA conformers including DNA G-quadruplex topologies as well as triplex DNA and duplex DNA. In general, G-quadruplex DNA shows a wide range of protection of hydrogens extending from ~12% to ~21% deuterium incorporation. Additionally, the DNA sequences selected to represent parallel, antiparallel, and hybrid G-quadruplex topologies exhibit slight differences in deuterium uptake levels which appear to loosely relate to overall conformer stability. Notably, the exchange level for one of the hybrid sequence sub topologies of G-quadruplex DNA (24 TTG) is significantly different (compared with the others studied here) despite the DNA sequences being highly comparable. For the quadruplex-forming sequences, correlation analysis suggests protection of base hydrogens involved in tetrad hydrogen bonding. For duplex DNA ~19% deuterium incorporation is observed while only ~16% is observed for triplex DNA. This increased protection of hydrogens may be due to the added backbone scaffolding and Hoogsteen base pairing of the latter species. These experiments lay the groundwork for future studies aimed at determining the structural source of this protection as well as the applicability of the approach for ascertaining different oligonucleotide folds, co-existing conformations, and/or overall conformer flexibility.
Competing Interests: Conflicts Disclosure The authors declare the following competing financial S.J.V. and P.L. have co-founded a start-up company, Invibragen Inc., to commercialize technologies involving vibrating sharp-edge spray ionization (VSSI). Declaration of interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Databáze: MEDLINE
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