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

Abstract

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.

Quercetin Exhibits Preferential Binding Interaction by Selectively Targeting HRAS1 I-Motif DNA-Forming Promoter Sequences

“…Here, in this research article, we have explored by extensive sets of experiments how Que (dietary flavonoid) interacts preferentially with HRAS1 iM noncanonical DNA structure with the intention of providing sharper viewpoints to develop innovative therapeutic agents for future disease management. From our previous studies, , it has been found that fisetin appears to be an efficient ligand for HRAS1 iM, VEGF iM, and morin considered to be an efficient ligand for HRAS2 iM DNA. This minor structural alteration appears to be critical for quercetin, fisetin, and morin’s capacity to interact differentially with different iM DNA.…”

“…While G-quadruplex configurations have received greater attention, there is growing curiosity in the I-Motif (iM), a noncanonical DNA construct generated inside cytosine-rich sequences of DNA and consisting of hemiprotonated C:C + base pairs bundled together in order to generate two hairpin structures. , iM DNA structures have been identified as prospective drug-binding targets. When contrasted with duplex DNA, iM DNA structures demonstrate a higher level of structural variation and heterogeneity .…”