高阶G-四链体端粒结构的聚合物特性：化学惰性拥挤剂的影响
Polymeric Properties of Higher-Order G-Quadruplex Telomeric Structures: Effects of Chemically Inert Crowders
AI总结：
本研究提出新型粗粒化G-四链体建模方法，发现长G-四链体多聚体为柔性大分子且拥挤环境会增强其卷曲倾向，为靶向G4的抗癌药物设计提供重要依据。
摘要：
G-四链体是人类基因组中普遍存在的非经典DNA结构，被认为在85%-90%的癌症发生发展中发挥关键作用。本文提出了一种新型粗粒化方法用于G-四链体建模，该方法可体现其结构柔性。我们将其应用于研究有无拥挤颗粒时G-四链体多聚体的聚合物特性，以模拟体内环境。研究发现，与文献中的部分观点相反，长G-四链体多聚体是相当柔性的聚合物大分子，其局部持久长度与单体尺寸相当，链刚度变化曲线符合良溶剂中真实聚合物的特征。此外，在体积分数最高达10%的拥挤环境中，G-四链体多聚体的卷曲倾向增强，测得的链刚度相应降低。准确阐明G4多聚体的聚合物特性对于理解其与靶向G4的抗癌药物的相互作用至关重要，从而可显著提升这类药物的设计水平与疗效。
英文摘要：
G-quadruplexes are non-canonical DNA structures rather ubiquitous in human genome, which are thought to play a crucial role in the development of 85-90 % of cancers. Here, we present a novel coarse-grained approach in modeling G-quadruplexes which accounts for their structural flexibility. We apply it to study the polymeric properties of G-quadruplex multimers, with and without crowder particles, to mimic in-vivo conditions. We find that, contrary to some suggestions found in the literature, long G-quadruplex multimers are rather flexible polymeric macromolecules, with a local persistence length comparable to monomer size, exhibiting chain stiffness variation profile consistent with a real polymer in good solvent. Moreover, in a crowded environment (up to 10% volume fraction), we report that G-quadruplex multimers exhibit an increased propensity for coiling, with a corresponding decrease in the measured chain stiffness. Accurately accounting for the polymeric properties of G4 multimers is crucial for understanding their interactions with anticancer G4-targeting drugs, thereby significantly enhancing the design and effectiveness of these drugs.
机构、总结、中文摘要均由AI分析而来，可能存在错误，请以论文正文为准。
