AI Article Synopsis
- cVSSI and HDX-MS were used to study various DNA forms, including G-quadruplexes, triplex, and duplex DNA, revealing their conformational properties.
- G-quadruplex DNA showed a 12% to 21% range in deuterium uptake, with different topologies having varying stability and protection levels of hydrogens.
- The findings suggest that G-quadruplex structures exhibit unique hydrogen protection characteristics, and the study sets the stage for future research on DNA conformations and flexibility.
Article Abstract
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.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11156224 | PMC |
| http://dx.doi.org/10.1016/j.ijms.2024.117231 | DOI Listing |
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