Prediction of fibril formation by early-stage amyloid peptide aggregation
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 th...
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| Format: | Article |
| Language: | English |
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Elsevier
2020-04-01
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| Series: | Journal of Pharmaceutical Analysis |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2095177919305817 |
| _version_ | 1819176872980774912 |
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| author | Jiaojiao Hu Huiyong Sun Haiping Hao Qiuling Zheng |
| author_facet | Jiaojiao Hu Huiyong Sun Haiping Hao Qiuling Zheng |
| author_sort | Jiaojiao Hu |
| collection | DOAJ |
| description | 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. Keywords: Mass spectrometry, Amyloid fibril, Early-stage oligomer, Peptide aggregation |
| first_indexed | 2024-12-22T21:17:40Z |
| format | Article |
| id | doaj.art-a3bfd8fea3d34dac8ba0b3c5e33bf2a9 |
| institution | Directory Open Access Journal |
| issn | 2095-1779 |
| language | English |
| last_indexed | 2024-12-22T21:17:40Z |
| publishDate | 2020-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Pharmaceutical Analysis |
| spelling | doaj.art-a3bfd8fea3d34dac8ba0b3c5e33bf2a92022-12-21T18:12:19ZengElsevierJournal of Pharmaceutical Analysis2095-17792020-04-01102194199Prediction of fibril formation by early-stage amyloid peptide aggregationJiaojiao Hu0Huiyong Sun1Haiping Hao2Qiuling Zheng3Department 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, ChinaDepartment of Medicinal Chemistry, 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, ChinaKey Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Tongjiaxiang #24, Nanjing, Jiangsu, 210009, China; State Key Laboratory of Natural Medicines, China Pharmaceutical University, Tongjiaxiang #24, Nanjing, Jiangsu, 210009, China; Corresponding author at: China Pharmaceutical University, Tongjiaxiang #24, Nanjing, Jiangsu, 210009, China.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; Corresponding author at: China Pharmaceutical University, Tongjiaxiang #24, Nanjing, Jiangsu, 210009, China.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. Keywords: Mass spectrometry, Amyloid fibril, Early-stage oligomer, Peptide aggregationhttp://www.sciencedirect.com/science/article/pii/S2095177919305817 |
| spellingShingle | Jiaojiao Hu Huiyong Sun Haiping Hao Qiuling Zheng Prediction of fibril formation by early-stage amyloid peptide aggregation Journal of Pharmaceutical Analysis |
| title | Prediction of fibril formation by early-stage amyloid peptide aggregation |
| title_full | Prediction of fibril formation by early-stage amyloid peptide aggregation |
| title_fullStr | Prediction of fibril formation by early-stage amyloid peptide aggregation |
| title_full_unstemmed | Prediction of fibril formation by early-stage amyloid peptide aggregation |
| title_short | Prediction of fibril formation by early-stage amyloid peptide aggregation |
| title_sort | prediction of fibril formation by early stage amyloid peptide aggregation |
| url | http://www.sciencedirect.com/science/article/pii/S2095177919305817 |
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