G-四链体作为毒品设计的有希望的目标，机会和挑战
Opportunities and challenges with G-quadruplexes as promising targets for drug design
影响因子:4.90000
分区:医学2区 / 药学2区
发表日期:2024 Nov
作者:
Victoria Sanchez-Martin
摘要
G-四链体（G4S）是在富含鸟嘌呤的核酸区域（DNA和RNA）中形成的二级结构。 G4在调节基因组区域显着富集，并且与重要的生物学过程有关，从端粒稳态和基因组不稳定性到转录和翻译。重要的是，G4与癌症，神经系统疾病以及病毒和微生物病原体的感染有关。越来越多的证据表明，尽管体内研究仍处于早期阶段，但G4s在设计新的诊断和治疗策略方面的潜力。本综述提供了描述G4S在人类疾病中的影响的最新摘要，以及基于G4靶向的不同方法在治疗方面的靶向。因此，在生物环境中对G4S的详细机理理解尚待解密。在诊所中，由于选择性率低，G4配体的药物样性质较差，因此将使用G4s作为治疗靶标受到阻碍。对G4S的未来研究可能会克服当前的方法论和介入局限性，并阐明疾病的发病机理和治疗中这些独特的结构元素。
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.