Simple and fast screening for structure-selective G-quadruplex ligands

Hashimoto, Yoshiki; Imagawa, Yoshiki; Nagano, Kaho; Maeda, Ryuichi; Nagahama, Naho; Torii, Takeru; Kinoshita, Natsuki; Takamiya, Nagisa; Kawauchi, Keiko; Tatesishi-Karimata, Hisae; Sugimoto, Naoki; Miyoshi, Daisuke

doi:10.1039/d3cc00556a

Cited by 4 publications

(1 citation statement)

References 21 publications

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“…These results indicate that both the length and sequences of loop regions of the i-motif had an important role in CV binding and its fluorescence emission. For G4 structures, the fluorescence level of CV with hTelo G4 ( F / F 0 = 53.0) and BCL2 G4 ( F / F 0 = 51.4) were relatively high, although the fluorescence enhancement was much smaller than that with BCL2 iM ( F / F 0 = 304.3), demonstrating higher selectivity of CV for BCL2 iM compared with the selectivity of CV for hTelo G4, as we previously reported 45 . Moreover, the hairpin DNA exhibited almost no change in fluorescence level.…”

Section: Resultssupporting

confidence: 77%

Theranostic approach to specifically targeting the interloop region of BCL2 i-motif DNA by crystal violet

Das,

Takahashi,

Ohyama

et al. 2023

Sci Rep

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Ligands that recognise specific i-motif DNAs are helpful in cancer diagnostics and therapeutics, as i-motif formation can cause cancer. Although the loop regions of i-motifs are promising targets for ligands, the interaction between a ligand and the loop regions based on sequence information remains unexplored. Herein, we investigated the loop regions of various i-motif DNAs to determine whether these regions specifically interact with fluorescent ligands. Crystal violet (CV), a triphenylmethane dye, exhibited strong fluorescence with the i-motif derived from the promoter region of the human BCL2 gene in a sequence- and structure-specific manner. Our systematic sequence analysis indicated that CV was bound to the site formed by the first and third loops through inter-loop interactions between the guanine bases present in these loops. As the structural stability of the BCL2 i-motif was unaffected by CV, the local stabilisation of the loops by CV could inhibit the interaction of transcription factors with these loops, repressing the BCL2 expression of MCF-7 cells. Our finding suggests that the loops of the i-motif can act as a novel platform for the specific binding of small molecules; thus, they could be utilised for the theranostics of diseases associated with i-motif DNAs.

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Section: Resultssupporting

confidence: 77%