Data for: Promising anti-amyloid behavior of cationic pyridylphenylene dendrimers: role of structural features and mechanism of action

The study describes the ability of cationic pyridylphenylene dendrimers of the second (G2), third (G3) and fourth (G4) generations to efficiently suppress the amyloid transformation of full-length ovine prion protein. The dendrimers are able to inhibit both the formation of the most toxic soluble oligomers and amyloid fibrils. monitor the secondary structure changes of PrP during oligomerization in the presence of dendrimers, circular dichroism spectroscopy (CD) was performed. CD molar elipticity.opj file collects raw circular dichroism data of the structures obtained when prevented prion protein oligomer formation by the dendrimers. Conversion CD to molar elipticity.xlsx file provides the information about molar elipticity calculation. The data show the formation of beta-sheet structure after incubation of PrP at 65 °C for 150 min without dendrimers, while addition of the dendrimers resulted in the mixed α/β structure. The formation of protein oligomers was monitored by dynamic light scattering (DLS). Sorokina_oligomers_dls.dts file consists of raw dynamic light scattering data to be opened in Zetasizer Software. The analysis revealed the formation of PrP oligomers of 21 nm in size, while a clear decrease in particle sizes was observed for G3. An absence of the conversion capacity of PrP-dendrimer complexes obtained when prevented amyloid fibril formation was tested using amyloid seeding assay. For the goal, the complexes resulted in the process of inhibition of amyloid fibril formation by the dendrimers were separated and thoroughly washed from the mixture and added as a seed to the native PrP. Seeding raw data.xslx file summarizes the raw thioflavine T fluorescence data and seeding.opj file represents the statistic calculation. It can be seen that even at low concentrations of 5 and 10 μM dendrimers significantly decrease the fluorescence intensity in comparison with that of the control. The highest impact was observed for G4 that inhibited the process at a concentration of 1 μM. The observations indicate the absence of conversion capacity in the protein-dendrimer complexes as they did not induce the conversion of the native PrP into abnormal form.本研究阐明了第二代（G2）、第三代（G3）与第四代（G4）阳离子吡啶亚苯树枝状大分子（cationic pyridylphenylene dendrimers）可高效抑制全长绵羊朊蛋白（full-length ovine prion protein）的淀粉样变性。这类树枝状大分子既能抑制毒性最强的可溶性寡聚体生成，也可阻断淀粉样纤维的形成。 为监测树枝状大分子存在时朊蛋白（PrP）寡聚化过程中的二级结构变化，本研究采用了圆二色谱（circular dichroism spectroscopy, CD）技术。CD摩尔椭圆率.opj文件收录了树枝状大分子阻断朊蛋白寡聚体生成时所得结构的原始圆二色谱数据；Conversion CD to molar ellipticity.xlsx文件则提供了摩尔椭圆率的计算相关信息。实验数据显示，未添加树枝状大分子的PrP在65℃孵育150分钟后会形成β-折叠结构，而添加树枝状大分子后则会形成混合的α/β结构。 通过动态光散射（dynamic light scattering, DLS）监测蛋白质寡聚体的生成情况。Sorokina_oligomers_dls.dts文件包含可通过Zetasizer软件读取的原始动态光散射数据。分析结果表明，未处理组出现了粒径为21 nm的PrP寡聚体，而G3处理组的粒径则出现明显减小。 为验证阻断淀粉样纤维生成所得的PrP-树枝状大分子复合物是否具备转化能力，本研究采用了淀粉样种子接种实验（amyloid seeding assay）。具体而言，将经树枝状大分子抑制淀粉样纤维生成所得的复合物分离并彻底洗涤后，作为种子添加至天然PrP中。Seeding raw data.xlsx汇总了硫黄素T（thioflavine T）荧光的原始数据，而seeding.opj文件则展示了统计计算结果。结果可见，即使在5 μM和10 μM的低浓度下，树枝状大分子即可显著降低荧光强度，其中以G4的效果最为显著，其在1 μM浓度下即可抑制该过程。上述结果表明，PrP-树枝状大分子复合物不具备转化能力，因其无法诱导天然PrP向异常构象转化。