Noncanonical DNA secondary structures as drug targets: The prospect of the i-motif

Under certain conditions, specific DNA sequences have the potential to adopt noncanonical secondary structures, such as i-motifs. Interestingly, these DNA stretches are not randomly located throughout the genome but rather frequently clustered in regulatory regions of oncogenes and in telomeres, the terminal regions of chromosomes. Recent evidences suggest that i-motif DNA structures exist in living cells and could be involved in a variety of biological processes, such as replication, regulation of oncogene expression, and telomere functions. Therefore, the targeting of i-motif DNA is an emerging research area in medicinal chemistry. Bringing these noncanonical structures into focus as targets for anticancer drug design and gene regulation processes could be crucial for a better understanding of their biological functions and to open the way to new, effective strategies for cancer treatment.