Characterizing Heparin Tetrasaccharides Binding to Amyloid-Beta Peptide
The aggregation of β-amyloid peptide (Aβ) is one potential cause for Alzheimer’s disease (AD). Heparin can either promote or inhibit Aβ aggregation. The sulfation pattern and chain size determine its binding affinity and its role. Using 2D-NMR analysis and molecular modelling, the binding motif of h...
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Frontiers Media S.A.
2022-02-01
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| Series: | Frontiers in Molecular Biosciences |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmolb.2022.824146/full |
| _version_ | 1819326777891225600 |
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| author | Xiang Zhou Yuanyuan Wang Wei Zheng Guangxiu Deng Fuyi Wang Lan Jin |
| author_facet | Xiang Zhou Yuanyuan Wang Wei Zheng Guangxiu Deng Fuyi Wang Lan Jin |
| author_sort | Xiang Zhou |
| collection | DOAJ |
| description | The aggregation of β-amyloid peptide (Aβ) is one potential cause for Alzheimer’s disease (AD). Heparin can either promote or inhibit Aβ aggregation. The sulfation pattern and chain size determine its binding affinity and its role. Using 2D-NMR analysis and molecular modelling, the binding motif of heparin oligoaccharides to Aβ was determined to be HexA-GlcNS-IdoA2S-GlcNS6S. Iduronic acid epimerization and 6-O-sulfation are key factors for the binding affinity, while 3-O-sulfation of Arixtra (heparin pentasaccharide) is not involved in the binding to Aβ. Hydrogen-deuterium exchange mass spectrometry (HDX-MS) was used to study the glycosaminoglycan (GAG)-peptide complex and identified V12HHQKL17 as the binding site of GAG at Aβ. Furthermore, an MTT assay was applied to evaluate the anti-Aβ fibril formation function of heparin tetrasaccharide, and indicated that the heparin tetrasaccharide with the defined sequence represents a promising inhibitor of Aβ aggregation. |
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| format | Article |
| id | doaj.art-c275268b50854043abf908ab78284b1d |
| institution | Directory Open Access Journal |
| issn | 2296-889X |
| language | English |
| last_indexed | 2024-12-24T13:00:21Z |
| publishDate | 2022-02-01 |
| publisher | Frontiers Media S.A. |
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| spelling | doaj.art-c275268b50854043abf908ab78284b1d2022-12-21T16:54:10ZengFrontiers Media S.A.Frontiers in Molecular Biosciences2296-889X2022-02-01910.3389/fmolb.2022.824146824146Characterizing Heparin Tetrasaccharides Binding to Amyloid-Beta PeptideXiang Zhou0Yuanyuan Wang1Wei Zheng2Guangxiu Deng3Fuyi Wang4Lan Jin5National Glycoengineering Research Center, Shandong Key Laboratory of Carbohydrate Chemistry and Glycobiology, Shandong University, Qingdao, ChinaBeijing National Laboratory for Molecular Sciences, CAS Key Laboratory of Analytical Chemistry for Living Biosystems Institute of Chemistry, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Beijing, ChinaBeijing National Laboratory for Molecular Sciences, CAS Key Laboratory of Analytical Chemistry for Living Biosystems Institute of Chemistry, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Beijing, ChinaNational Glycoengineering Research Center, Shandong Key Laboratory of Carbohydrate Chemistry and Glycobiology, Shandong University, Qingdao, ChinaCollege of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, ChinaNational Glycoengineering Research Center, Shandong Key Laboratory of Carbohydrate Chemistry and Glycobiology, Shandong University, Qingdao, ChinaThe aggregation of β-amyloid peptide (Aβ) is one potential cause for Alzheimer’s disease (AD). Heparin can either promote or inhibit Aβ aggregation. The sulfation pattern and chain size determine its binding affinity and its role. Using 2D-NMR analysis and molecular modelling, the binding motif of heparin oligoaccharides to Aβ was determined to be HexA-GlcNS-IdoA2S-GlcNS6S. Iduronic acid epimerization and 6-O-sulfation are key factors for the binding affinity, while 3-O-sulfation of Arixtra (heparin pentasaccharide) is not involved in the binding to Aβ. Hydrogen-deuterium exchange mass spectrometry (HDX-MS) was used to study the glycosaminoglycan (GAG)-peptide complex and identified V12HHQKL17 as the binding site of GAG at Aβ. Furthermore, an MTT assay was applied to evaluate the anti-Aβ fibril formation function of heparin tetrasaccharide, and indicated that the heparin tetrasaccharide with the defined sequence represents a promising inhibitor of Aβ aggregation.https://www.frontiersin.org/articles/10.3389/fmolb.2022.824146/fullheparinβ-amyloid peptideinteractionNMRhydrogen/deuterium exchange mass spectrometry |
| spellingShingle | Xiang Zhou Yuanyuan Wang Wei Zheng Guangxiu Deng Fuyi Wang Lan Jin Characterizing Heparin Tetrasaccharides Binding to Amyloid-Beta Peptide Frontiers in Molecular Biosciences heparin β-amyloid peptide interaction NMR hydrogen/deuterium exchange mass spectrometry |
| title | Characterizing Heparin Tetrasaccharides Binding to Amyloid-Beta Peptide |
| title_full | Characterizing Heparin Tetrasaccharides Binding to Amyloid-Beta Peptide |
| title_fullStr | Characterizing Heparin Tetrasaccharides Binding to Amyloid-Beta Peptide |
| title_full_unstemmed | Characterizing Heparin Tetrasaccharides Binding to Amyloid-Beta Peptide |
| title_short | Characterizing Heparin Tetrasaccharides Binding to Amyloid-Beta Peptide |
| title_sort | characterizing heparin tetrasaccharides binding to amyloid beta peptide |
| topic | heparin β-amyloid peptide interaction NMR hydrogen/deuterium exchange mass spectrometry |
| url | https://www.frontiersin.org/articles/10.3389/fmolb.2022.824146/full |
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