Department of Applied Sciences, Maharaja Surajmal Institute of Technology, GGSIP University, New Delhi 110058, India.
Department of Chemistry, Shri Varshney College, Aligarh, India.
Int J Biol Macromol. 2022 Oct 31;219:414-427. doi: 10.1016/j.ijbiomac.2022.07.248. Epub 2022 Aug 5.
Guanine-rich DNA sequences may fold back into non-canonical four-stranded secondary structures termed as G-quadruplexes. The role of G-quadruplexes has already been well established in different diseases like cancer, neurological and viral disorders etc. Also, several small molecules have been reported, which can influence the involvement of G-quadruplexes either through stabilization or destabilization in the cellular environment. Growing statistics have associated G-quadruplex assemblies to a discrete biological process in vivo, including DNA replication, transcription, genomic stability, and epigenetic regulation. DNA G-quadruplex existence in human telomere is well recognized attractive target for anticancer drugs. G-quadruplex-interactive ligands have been known to prevent telomerase access as well as telomere capping. To the best of our understanding, the role of G-quadruplexes in virology, neuropharmacology, cancer progression and its treatment has not been discussed on a single platform till date. This review aims to enhance our knowledge regarding these magical sticky quadruplex structures, which have been quite significantly proved to be the part of many cellular processes along with their established in vivo existence. Understanding regarding stabilizing or destabilizing ligands of these multistranded guanine quadruplex structures might be proved as the facilitator of drug discovery process for many incurable diseases in future.
富含鸟嘌呤的 DNA 序列可能会折叠成非典型的四链二级结构，称为 G-四链体。G-四链体在癌症、神经和病毒等多种疾病中的作用已经得到充分证实。此外，已经报道了几种小分子，它们可以通过在细胞环境中稳定或不稳定来影响 G-四链体的参与。越来越多的统计数据将 G-四链体组装与体内特定的生物学过程联系起来，包括 DNA 复制、转录、基因组稳定性和表观遗传调控。人类端粒中的 DNA G-四链体的存在是一种很有吸引力的抗癌药物靶点。已经知道 G-四链体相互作用配体可以防止端粒酶进入和端粒封端。据我们所知，G-四链体在病毒学、神经药理学、癌症进展及其治疗中的作用尚未在单一平台上进行讨论。这篇综述旨在增强我们对这些神奇粘性四链体结构的认识，这些结构已经被证明是许多细胞过程的一部分，并且它们在体内的存在已经得到证实。对这些多链鸟嘌呤四链体结构的稳定或不稳定配体的理解，可能被证明是未来许多不治之症药物发现过程的促进剂。
