基于G4-配体的DNA模拟酶在生物传感中的发展与应用

鸟苷酸-四联体DNA (G4 DNA)是由富含串联重复鸟苷酸(G)的DNA或RNA序列形成的G4片层,并堆叠而成一类独特的核酸二级结构。G4 DNA结合多种特异性配体可形成具有催化过氧化氢活性的G4 DNA模拟酶(G4 DNAzyme)。由于G4 DNAzyme存在着序列构成简便灵活、适合多样传感平台检测等特点,其在新型生物传感方法研发、医学检测新技术研究等领域中应用前景广阔。本文主要依据G4 DNA结合配体的不同,对近年来新发展出的G4 DNAzyme进行分类与回顾,归纳为含氯化血红素(hemin)的G4-Hemin DNAzyme与非G4-Hemin DNAzyme。前者是目前G4 DNA模拟酶的研究主流——本文主要归纳了G4-Hemin DNAzyme在金属阳离子、生物小分子及生物大分子的检测分析方向上所取得的重要研究进展,并阐述其在生物传感领域的影响和优势;后者中的配体则主要包括金属阳离子N-甲基吗啡啉(4-methylmorpholine,NMM)、硫磺素T(thioflavin T,ThT)及新型金属配体(Cu²⁺＼Ce^{3 +})等。本文归纳其构成多样的G4 DNAzyme在生物传感领域、医学检测方向的最新研究进展与应用实例。全文最后对G4 DNAzyme的未来研究方向,以及进一步提高其催化检测灵敏度和准确性的积极作用提出展望。

Development and Application of G4 DNAzyme Based on Different Ligands in Biosensing

Guanine (G)-tetramer DNA (G4-DNA) is a unique secondary structure of nucleic acid. It is formed by stacking G-tetramer in G-rich DNA or RNA sequences. In recent years, the G4-DNA mimicking enzyme (G4 DNAzyme), which catalyzes hydrogen peroxide activity, has been shown to undergo G4-DNA binding to various specific ligands. Because of its simple, flexible sequence structure and suitability for detecting various sensing platforms, the G4 DNAzyme has been widely reported in the research of new biosensing methods and new medical detection technologies, where it has bright prospects. Based on the different types of binding ligands, this study mainly provides the classification and review of the G4 DNAzymes developed in recent years; G4-hemin DNAzymes and non-G4-hemin DNAzymes are also classified. The G4-hemin DNAzyme has been the main focus in G4 DNAzyme research. We concluded that the G4-hemin DNAzyme has facilitated significant progress in the detection and analysis of metal cations, small biomolecules, and biomacromolecules. Its influence and advantages in the field of biosensing was also summarized. Our coverage of non-G4-hemin DNAzymes mainly includes the latest research progress and application examples of NMM, ThT, and metal cation ligands in such important applications as biomedical sensors and medical detection. Future studies on G4 DNAzymes and their role in improving the sensitivity and accuracy of the catalytic detection of such nucleic acid mimics were also discussed.