Abstract
G-quadruplex is a special secondary structure of nucleic acids in guanine-rich sequences of genome. G-quadruplexes have been proved to be involved in the regulation of replication, DNA damage repair, and transcription and translation of oncogenes or other cancer-related genes. Therefore, targeting G-quadruplexes has become a novel promising anti-tumor strategy. Different kinds of small molecules targeting the G-quadruplexes have been designed, synthesized, and identified as potential anti-tumor agents, including molecules directly bind to the G-quadruplex and molecules interfering with the binding between the G-quadruplex structures and related binding proteins. This review will explore the feasibility of G-quadruplex ligands acting as anti-tumor drugs, from basis to application. Meanwhile, since helicase is the most well-defined G-quadruplex-related protein, the most extensive research on the relationship between helicase and G-quadruplexes, and its meaning in drug design, is emphasized.
Highlights
Cancer is one of the major diseases that pose a serious threat to human life and health
G-quadruplex structure can persist through multiple mitotic divisions, which might increase the risk of DNA double-strand breaks [130]
N-methylated modification to mimic the interactions between cations and the anion central channel is a common strategy for G-quadruplex ligand optimization
Summary
Cancer is one of the major diseases that pose a serious threat to human life and health. Developing novel drugs that interact with nucleic acids using novel strategies is a significant consideration in research. According to this, finding anti-tumor agents that target the G-quadruplex structure in nucleic acids has been raised as an alternative drug development strategy, since it might increase the selectivity and specificity of drugs on certain genome regions. Compared to developing inhibitors for a specific enzyme or protein, selective interaction with the G-quadruplex structures in particular genome regions is difficult to achieve. Helicases play essential roles in nucleic acid metabolism by facilitating cellular processes including replication, recombination, DNA repair, and transcription [23,24,25]. We hope to focus on the progress made in helicase-related leading compounds to give a comprehensive view of this field
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