Jerzy Haber Institute of Catalysis and Surface Chemistry, Polish Academy of Sciences, ul. Niezapominajek 8, 30239 Cracow, Poland.
Molecules. 2024 Oct 2;29(19):4683. doi: 10.3390/molecules29194683.
This article provides a comprehensive examination of non-canonical DNA structures, particularly focusing on G-quadruplexes (G4s) and i-motifs. G-quadruplexes, four-stranded structures formed by guanine-rich sequences, are stabilized by Hoogsteen hydrogen bonds and monovalent cations like potassium. These structures exhibit diverse topologies and are implicated in critical genomic regions such as telomeres and promoter regions of oncogenes, playing significant roles in gene expression regulation, genome stability, and cellular aging. I-motifs, formed by cytosine-rich sequences under acidic conditions and stabilized by hemiprotonated cytosine-cytosine (C:C+) base pairs, also contribute to gene regulation despite being less prevalent than G4s. This review highlights the factors influencing the stability and dynamics of these structures, including sequence composition, ionic conditions, and environmental pH. Molecular dynamics simulations and high-resolution structural techniques have been pivotal in advancing our understanding of their folding and unfolding mechanisms. Additionally, the article discusses the therapeutic potential of small molecules designed to selectively bind and stabilize G4s and i-motifs, with promising implications for cancer treatment. Furthermore, the structural properties of these DNA forms are explored for applications in nanotechnology and molecular devices. Despite significant progress, challenges remain in observing these structures in vivo and fully elucidating their biological functions. The review underscores the importance of continued research to uncover new insights into the genomic roles of G4s and i-motifs and their potential applications in medicine and technology. This ongoing research promises exciting developments in both basic science and applied fields, emphasizing the relevance and future prospects of these intriguing DNA structures.
本文全面探讨了非经典 DNA 结构，特别是 G-四链体（G4s）和 i- 型结构。G-四链体是由富含鸟嘌呤的序列形成的四链结构，由 Hoogsteen 氢键和单价阳离子（如钾）稳定。这些结构具有多种拓扑结构，存在于端粒和致癌基因启动子等关键基因组区域，在基因表达调控、基因组稳定性和细胞衰老中发挥重要作用。在酸性条件下，由富含胞嘧啶的序列形成的 i- 型结构，并由半质子化的胞嘧啶-胞嘧啶（C:C+）碱基对稳定，尽管不如 G4s 常见，但也对基因调控有贡献。本文强调了影响这些结构稳定性和动态性的因素，包括序列组成、离子条件和环境 pH 值。分子动力学模拟和高分辨率结构技术对深入了解它们的折叠和展开机制至关重要。此外，本文还讨论了设计用于选择性结合和稳定 G4s 和 i- 型结构的小分子的治疗潜力，这对癌症治疗具有广阔的前景。此外，还探讨了这些 DNA 形式的结构特性在纳米技术和分子器件中的应用。尽管已经取得了重大进展，但在体内观察这些结构并充分阐明其生物学功能仍然存在挑战。本文强调了继续研究的重要性，以揭示 G4s 和 i- 型结构在基因组中的作用及其在医学和技术中的潜在应用的新见解。这项正在进行的研究有望在基础科学和应用领域取得令人兴奋的进展，强调了这些有趣的 DNA 结构的相关性和未来前景。
