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- W3005463398 abstract "It is now well established that the anionic porphyrin, N-methylmesoporphyrin IX (NMM) exhibits binding selectivity for the DNA G-quadruplex (G4) over other DNA secondary structures. Specifically, NMM binds, promotes and stabilizes a K+-induced mixed-hybrid G4 conformation, and demonstrates little affinity for the antiparallel DNA G-quadruplex conformation promoted in a sodium buffer. In solution, it is generally believed that the binding site for NMM resides within the terminal lateral loop of the DNA G-quadruplex. However, specific interactions or conformational switching of this loop between mixed-hybrid conformations has not been explored in any great depth. Using a combination of circular dichroism (CD) and a series of guanine substituted DNA telomeric sequences, where the fluorescent guanine analog (6MI) substitutes guanine residues anchoring the terminal lateral loop, we have mapped the mixed-hybrid conformational switching of the DNA G-quadruplex with NMM binding. Differences in fluorescence intensity quenching of 6MI substituted guanine residues, combined with CD measurements, clearly show those guanine positions that actively participate in the lateral loop conformational switch. In particular, we have identified the G7-6MI guanine position as exhibiting a key role in this cooperative conformational switching process. Fluorescence lifetime studies suggest that the observed quenching of fluorescence intensities arises predominantly from a static quenching mechanism arising presumably from enhanced base-base stacking. Our studies demonstrate the significance of specific guanine residues in modulating conformational populations, and their importance for promoting potential ligand binding sites. (Supported by NIH-SCORE GM 095437-04.)" @default.
- W3005463398 created "2020-02-14" @default.
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- W3005463398 date "2020-02-01" @default.
- W3005463398 modified "2023-09-26" @default.
- W3005463398 title "Mapping Lateral Loop Conformational Switching of the Telomeric DNA G-Quadruplex on NMM Prophyrin Binding Using Fluorescent Guanine Analogs" @default.
- W3005463398 doi "https://doi.org/10.1016/j.bpj.2019.11.530" @default.
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