Hu Jiaojiao, Sun Huiyong, Hao Haiping, Zheng Qiuling
Department of Pharmaceutical Analysis, School of Pharmacy, China Pharmaceutical University, Tongjiaxiang #24, Nanjing, Jiangsu, 210009, China.
State Key Laboratory of Natural Medicines, China Pharmaceutical University, Tongjiaxiang #24, Nanjing, Jiangsu, 210009, China.
J Pharm Anal. 2020 Apr;10(2):194-199. doi: 10.1016/j.jpha.2019.12.002. Epub 2019 Dec 13.
Amyloid fibrils are found in systemic amyloidosis diseases such as Alzheimer's disease, Parkinson's disease, and type II diabetes. Currently, these diseases are diagnosed by observation of fibrils or plaques, which is an ineffective method for early diagnosis and treatment of disease. The goal of this study was to develop a simple and quick method to predict the possibility and speed of fibril formation before its occurrence. Oligomers generated from seven representative peptide segments were first isolated and detected by ion-mobility mass spectrometry (IM-MS). Then, their assemblies were disrupted using formic acid (FA). Interestingly, oligomers that showed small ion intensity changes upon FA addition had rapid fibril formation. By contrast, oligomers that had large ion intensity changes generated fibrils slowly. Two control peptides (aggregation/no fibrils and no aggregation/no fibrils) did not show changes in their ion intensities, which confirmed the ability of this method to predict amyloid formation. In summary, the developed method correlated MS intensity ratio changes of peptide oligomers on FA addition with their amyloid propensities. This method will be useful for monitoring peptide/protein aggregation behavior and essential for their mechanism studies.
淀粉样纤维存在于系统性淀粉样变性疾病中，如阿尔茨海默病、帕金森病和II型糖尿病。目前，这些疾病通过观察纤维或斑块来诊断，这对于疾病的早期诊断和治疗是一种无效的方法。本研究的目的是开发一种简单快速的方法，在纤维形成之前预测其形成的可能性和速度。首先通过离子淌度质谱（IM-MS）分离并检测由七个代表性肽段产生的寡聚体。然后，使用甲酸（FA）破坏它们的组装。有趣的是，添加FA后离子强度变化小的寡聚体纤维形成迅速。相比之下，离子强度变化大的寡聚体纤维形成缓慢。两种对照肽（聚集/无纤维和无聚集/无纤维）的离子强度没有变化，这证实了该方法预测淀粉样蛋白形成的能力。总之，所开发的方法将添加FA后肽寡聚体的质谱强度比变化与其淀粉样蛋白倾向相关联。该方法将有助于监测肽/蛋白质的聚集行为，对其机制研究至关重要。
