School of Pharmacy, Shandong Second Medical University, Weifang, 261053, China.
State Key Laboratory of Supramolecular Structure and Materials, Center for Supramolecular Chemical Biology, Institute of Theoretical Chemistry, College of Chemistry, Jilin University, 2699 Qianjin Street, Changchun, China.
Talanta. 2024 Dec 1;280:126685. doi: 10.1016/j.talanta.2024.126685. Epub 2024 Aug 12.
Protein amyloid fibrillation is linked to a wide range of neurodegenerative diseases. Protein oligomer is an intermediate substance in the process of fibrillation, which is neurotoxic and formed by the aggregation of protein molecules under physiological stress. Early detection of protein oligomers could make timely intervention of protein fibrillation related diseases. Therefore, it is crucial to develop efficient inhibitors and probes for monitoring amyloid fibril formation. In this study, we developed a novel amyloid inhibitor quinoline yellow (QY), which was proved to be effective in inhibiting insulin protein fibrillation as demonstrated by fluorescence, morphology characterization and circular dichroism. When QY binds to insulin, it exerts inhibitory effects on the nucleation process and effectively impedes the formation of fibrillar fibrils. In addition, we present the application of surface-enhanced Raman spectroscopy (SERS) as an extremely sensitive technique for identifying amyloid oligomers. The investigation employed the probe QY, which demonstrated a linear reaction for identifying oligomers in the concentration range of 1.0-58.0 μM. Impressively, it showcased an exceptionally sensitive detection threshold of 0.2 μM. And also illustrating the binding sites and interaction mechanisms between small molecules of QY and insulin by SERS. The aforementioned methodology was also employed for the identification of insulin oligomers in human serum samples. Thereby, the proposed approach presenting a promising avenue with extensive implications in the realms of pharmaceutical exploration and disease diagnosis.
蛋白质淀粉样纤维形成与多种神经退行性疾病有关。蛋白质低聚物是纤维形成过程中的中间物质，具有神经毒性，是在生理应激下蛋白质分子聚集形成的。早期检测蛋白质低聚物可以及时干预与蛋白质纤维形成相关的疾病。因此，开发有效的抑制剂和探针来监测淀粉样纤维的形成至关重要。在这项研究中，我们开发了一种新型的淀粉样抑制剂喹啉黄（QY），通过荧光、形态特征和圆二色性证实其能有效抑制胰岛素蛋白纤维形成。当 QY 与胰岛素结合时，它对成核过程产生抑制作用，并有效地阻止纤维状纤维的形成。此外，我们还提出了表面增强拉曼光谱（SERS）作为一种非常灵敏的技术来识别淀粉样低聚物。该研究采用了探针 QY，证明其在 1.0-58.0 μM 的浓度范围内对寡聚体具有线性反应。令人印象深刻的是，它表现出 0.2 μM 的超低检测限。同时，SERS 还说明了小分子 QY 与胰岛素之间的结合位点和相互作用机制。还利用上述方法鉴定了人血清样本中的胰岛素寡聚体。因此，所提出的方法在药物探索和疾病诊断领域具有广阔的应用前景。
