G-四链体作为药物设计中有潜力的靶点的机遇与挑战
Opportunities and challenges with G-quadruplexes as promising targets for drug design
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影响因子:4.9
分区:医学2区 / 药学2区
发表日期:2024 Nov
作者:
Victoria Sanchez-Martin
DOI:
10.1080/17460441.2024.2404230
摘要
G-四链体（G4）是由富含鸟嘌呤的核酸（DNA和RNA）区域形成的二级结构。G4在调控基因组区域富集，与端粒稳态、基因组不稳定、转录和翻译等重要生物过程相关。值得注意的是，G4与癌症、神经疾病以及病毒和微生物感染等健康和疾病密切相关。越来越多的证据表明G4在设计新诊断和治疗策略中的潜力，尽管体内研究仍处于早期阶段。本综述更新了关于G4在人类疾病中的作用以及基于G4靶向的治疗方法的文献。大部分研究是在体外和描述性层面进行的，因此，G4在生物学背景下的详细机制尚待解明。在临床应用中，G4作为治疗靶点受到限制，主要是由于G4配体的选择性低和药物性质差。未来的研究可能克服目前的方法学和干预局限，更好地揭示这些独特结构元素在疾病发生和治疗中的作用。
Abstract
G-quadruplexes (G4s) are secondary structures formed in guanine-rich regions of nucleic acids (both DNA and RNA). G4s are significantly enriched at regulatory genomic regions and are associated with important biological processes ranging from telomere homeostasis and genome instability to transcription and translation. Importantly, G4s are related to health and diseases such as cancer, neurological diseases, as well as infections with viruses and microbial pathogens. Increasing evidence suggests the potential of G4s for designing new diagnostic and therapeutic strategies although in vivo studies are still at early stages.This review provides an updated summary of the literature describing the impact of G4s in human diseases and different approaches based on G4 targeting in therapy.Within the G4 field, most of the studies have been performed in vitro and in a descriptive manner. Therefore, detailed mechanistic understanding of G4s in the biological context remains to be deciphered. In clinics, the use of G4s as therapeutic targets has been hindered due to the low selectivity profile and poor drug-like properties of G4 ligands. Future research on G4s may overcome current methodological and interventional limitations and shed light on these unique structural elements in the pathogenesis and treatment of diseases.