Journal
FRONTIERS IN PHARMACOLOGY
Volume 14, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fphar.2023.1136251
Keywords
i-motif; biological activities; molecular mechanism; ligand compounds; oncogene; telomere; gene-targeted therapy
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i-motifs, as non-canonical secondary structures of cytosine-rich nucleic acids, can form under specific conditions. They have been identified in the human genome and play important roles in biological regulation. Due to their physicochemical properties, i-motif structures have become new targets for drug development. This review discusses the characteristics and mechanisms of i-motifs located in gene promoters, the interaction with small molecule ligands, their effects on gene expression, diseases associated with i-motifs, and recent advances in their applications.
As non-canonical nucleic acid secondary structures consisting of cytosine-rich nucleic acids, i-motifs can form under certain conditions. Several i-motif sequences have been identified in the human genome and play important roles in biological regulatory functions. Due to their physicochemical properties, these i-motif structures have attracted attention and are new targets for drug development. Herein, we reviewed the characteristics and mechanisms of i-motifs located in gene promoters (including c-myc, Bcl-2, VEGF, and telomeres), summarized various small molecule ligands that interact with them, and the possible binding modes between ligands and i-motifs, and described their effects on gene expression. Furthermore, we discussed diseases closely associated with i-motifs. Among these, cancer is closely associated with i-motifs since i-motifs can form in some regions of most oncogenes. Finally, we introduced recent advances in the applications of i-motifs in multiple areas.
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