DNA intercalated motif (i-Motif) (i-motif)

DNA i-motifs are non-canonical, four-stranded nucleic acid structures formed in cytosine-rich regions of the genome, characterized by the intercalation of hemi-protonated cytosine-cytosine (C:C+) base pairs [1][3]. These structures exist in a dynamic equilibrium with the standard double-stranded duplex DNA and are frequently located within regulatory regions such as gene promoters and telomeric sequences [2]. In biological systems, the transition between the duplex and i-motif states acts as a molecular switch that regulates the transcription of key oncogenes, including c-MYC, BCL2, and KRAS [4]. Therapeutic intervention typically involves the use of small molecules designed to selectively bind and stabilize the i-motif structure, thereby preventing its reversion to duplex DNA and inhibiting gene expression [2][3]. However, a major challenge in drug development is achieving high selectivity for the i-motif over the ubiquitous duplex DNA to avoid off-target genotoxicity [3]. Targeting these structures represents a promising strategy for precision oncology, though further research is required to manage potential safety concerns related to widespread DNA binding [4].

Other names

i-DNAIntercalated motifC-rich DNA structureDouble-stranded DNAdsDNAC-quadruplex

Small molecule stabilization of the i-motif structure to inhibit the transcription of associated oncogenes by preventing the formation of the duplex DNA state.