Discriminating the conformation of G4 DNA by SANS.

Guanine-­rich DNA sequences are prone to fold into stable helical four­-stranded structures called G­quadruplexes (G4). These systems have drawn the attention of a number of scientists in both basic and applied research fields, including structural biophysics, cancer biology, novel therapeutics through to nanotechnology. And most importantly, G4s have been proposed as selective and effective therapeutic anticancer targets. However, the intrinsic polymorphism of G4s makes very challenging the prediction of the architectural folds encoded in guanine-rich DNA sequences. Up to now circular dichroism and NMR techniques have been extensively used to investigate the topology of G4 structures. Here we propose to investigate three G4s, selected on the basis of their conformational properties, to develop proof of concept for methodology for characterizing G4 architecture from SANS signature alone.

富含鸟嘌呤的DNA序列易于折叠形成稳定的螺旋四链结构，这类结构被称为G-四链体（G-quadruplexes，G4）。这类结构在基础与应用研究领域均受到众多科研工作者的关注，研究范畴覆盖结构生物物理学、癌症生物学、新型治疗方案开发乃至纳米技术等多个方向。尤为重要的是，G4已被提出为兼具选择性与高效性的抗肿瘤治疗靶点。然而，G4固有的多态性使得富含鸟嘌呤DNA序列所编码的结构折叠模式的预测极具挑战性。迄今为止，圆二色谱（circular dichroism）与核磁共振（NMR）技术已被广泛应用于G4结构拓扑特征的探究。本研究拟选取三种基于构象特性筛选得到的G4，以开发仅通过小角中子散射（Small Angle Neutron Scattering，SANS）特征即可表征G4结构的方法学概念验证方案。