人类端粒 G 四链体 (G4) 的稳定性与癌症疾病直接相关。人类端粒主要与侧翼核碱基相关，这会影响 G4 的稳定性。因此，在本研究中，在模拟正常和癌症 KCl 微环境的不同浓度 KCl 中，研究了侧翼核碱基的化学性质、数量和位置对 G4 结构和稳定性的影响。添加侧翼核碱基不会改变 G4 拓扑结构。然而，仅存在一个侧翼核碱基就会破坏端粒 G4 的稳定性。这种不稳定效应对于胸腺嘧啶比腺嘌呤侧翼核碱基更为突出，可能是由于胸腺嘧啶形成了分子间 G4 拓扑结构。有趣的是，与腺嘌呤相比，在胸腺嘧啶侧翼核碱基存在的情况下，端粒 G4 的稳定性变化对与正常和癌性微环境相关的 KCl 浓度敏感。与 3' 端相比，侧翼核碱基对 5' 端的影响更大，在类似于正常微环境而不是癌性微环境的 KCl 浓度中尤其明显。这些发现表明侧翼核碱基对端粒 G4 的影响在与正常和癌性微环境相关的 KCl 盐中是不同的。这项研究可能有助于在分子水平上深入了解 G4 在正常和癌性 KCl 盐条件下端粒长度调节中的作用。

The stability of the human telomere G-quadruplex (G4) is directly linked to cancer disease. The human telomere is mostly associated with the flanking nucleobases, which can affect the stability of G4. Hence, in this study, the effect of the flanking nucleobases in the context of their chemical nature, number, and position on the structure and stability of G4 has been investigated in varying concentrations of KCl mimicking the normal and cancer KCl microenvironments. The addition of flanking nucleobases does not alter the G4 topology. However, the presence of merely a single flanking nucleobase destabilizes the telomeric G4. This destabilizing effect is more prominent for thymine than adenine flanking nucleobase, probably due to the formation of the intermolecular G4 topology by thymine. Interestingly, the change in the stability of the telomeric G4 in the presence of thymine flanking nucleobase is sensitive to the concentration of KCl relevant to the normal and cancerous microenvironments, in contrast to adenine. Flanking nucleobases have a greater impact at the 5' end compared to the 3' end, particularly noticeable in KCl concentrations resembling the normal microenvironment rather than the cancerous one. These findings indicate that the effect of the flanking nucleobases on telomeric G4 is different in the KCl salt relevant to normal and cancerous microenvironments. This study may be helpful in attaining molecular-level insight into the role of G4 in telomeric length regulation under normal and cancerous KCl salt conditions.