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dc.contributor.authorSoenarjo, A Larasati
dc.contributor.authorLan, Zhihao
dc.contributor.authorSazanovich, Igor V.
dc.contributor.authorChan, Yee San
dc.contributor.authorRingholm, Magnus
dc.contributor.authorJha, Ajay
dc.contributor.authorKlug, David R.
dc.date.accessioned2024-01-12T14:15:32Z
dc.date.available2024-01-12T14:15:32Z
dc.date.issued2023-08-30
dc.description.abstractA class of DNA folds/structures known collectively as G-quadruplexes (G4) commonly forms in guanine-rich areas of genomes. G4-DNA is thought to have a functional role in the regulation of gene transcription and telomerase-mediated telomere maintenance and, therefore, is a target for drugs. The details of the molecular interactions that cause stacking of the guanine-tetrads are not well-understood, which limits a rational approach to the drugability of G4 sequences. To explore these interactions, we employed electron-vibration-vibration two-dimensional infrared (EVV 2DIR) spectroscopy to measure extended vibrational coupling spectra for a parallel-stranded G4-DNA formed by the Myc2345 nucleotide sequence. We also tracked the structural changes associated with G4-folding as a function of K<sup>+</sup>-ion concentration. To classify the structural elements that the folding process generates in terms of vibrational coupling characteristics, we used quantum-chemical calculations utilizing density functional theory to predict the coupling spectra associated with given structures, which are compared against the experimental data. Overall, 102 coupling peaks are experimentally identified and followed during the folding process. Several phenomena are noted and associated with formation of the folded form. This includes frequency shifting, changes in cross-peak intensity, and the appearance of new coupling peaks. We used these observations to propose a folding sequence for this particular type of G4 under our experimental conditions. Overall, the combination of experimental 2DIR data and DFT calculations suggests that guanine-quartets may already be present before the addition of K<sup>+</sup>-ions, but that these quartets are unstacked until K<sup>+</sup>-ions are added, at which point the full G4 structure is formed.en_US
dc.identifier.citationSoenarjo, Lan, Sazanovich, Chan, Ringholm, Jha, Klug. The Transition from Unfolded to Folded G-Quadruplex DNA Analyzed and Interpreted by Two-Dimensional Infrared Spectroscopy. Journal of the American Chemical Society. 2023;145(36):19622-19632en_US
dc.identifier.cristinIDFRIDAID 2179809
dc.identifier.doi10.1021/jacs.3c04044
dc.identifier.issn0002-7863
dc.identifier.issn1520-5126
dc.identifier.urihttps://hdl.handle.net/10037/32466
dc.language.isoengen_US
dc.publisherACS Publicationsen_US
dc.relation.journalJournal of the American Chemical Society
dc.rights.accessRightsopenAccessen_US
dc.rights.holderCopyright 2023 The Author(s)en_US
dc.rights.urihttps://creativecommons.org/licenses/by/4.0en_US
dc.rightsAttribution 4.0 International (CC BY 4.0)en_US
dc.titleThe Transition from Unfolded to Folded G-Quadruplex DNA Analyzed and Interpreted by Two-Dimensional Infrared Spectroscopyen_US
dc.type.versionpublishedVersionen_US
dc.typeJournal articleen_US
dc.typeTidsskriftartikkelen_US
dc.typePeer revieweden_US


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Attribution 4.0 International (CC BY 4.0)
Med mindre det står noe annet, er denne innførselens lisens beskrevet som Attribution 4.0 International (CC BY 4.0)