DNA G-四链体(G4)是富含鸟嘌呤的单链DNA序列，在生理溶液环境下，通过Hoogsteen氢键结合，并被单价阳离子稳定，自发折叠形成的一种球状四链体DNA二级结构。G4s在端粒和癌基因启动子序列中大量存在，与癌症的发生发展密切相关，是有潜力的抗癌药物研究新靶点。天然产物长期以来一直是抗癌药物发现的重要来源。近年来，以DNAG4s为靶点的天然药物研究取得了重大进展，许多DNA G4s被证实为天然产物的有效作用靶点，包括MYC-G4、KRAS-G4、PDGFR-β-G4、BCL-2-G4、VEGF-G4和端粒G4等。该文系统总结了天然小分子化合物识别DNA G4s的分子机制和研究进展，进而讨论了开发G4靶向药物面临的机遇和挑战，为天然抗癌创新药物研发提供了重要的参考。
Research progress in targeting DNA G-quadruplexes using natural products
DNA G-quadruplex(G4)is a guanine-rich single-stranded DNA sequence that spontaneously folds into a spherical four-stranded DNA secondary structure in oncogene promoter sequences and telomeres.G4s are highly associated with the occurrence and development of cancer and have emerged as promising anticancer targets.Natural products have long been important sources of antican-cer drug development.In recent years,significant progress has been made in the discovery of natural drugs targeting DNA G4s,with many DNA G4s have been confirmed as promising targets of natural products,including MYC-G4,KRAS-G4,PDGFR-β-G4,BCL-2-G4,VEGF-G4,and telomeric G4.This review summarizes the research progress in discovering natural small molecules that target DNA G4s and their binding mechanisms.It also discusses the opportunities of and challenges in developing drugs targeting DNA G4s.This review will serve as a valuable reference for the research on natural products,particularly in the development of novel antitumor medica-tions.
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