Characterizing Heparin Tetrasaccharides Binding to Amyloid-Beta Peptide

Frontiers in Molecular Biosciences

Yuanyuan Wang¹  Wei Zheng¹  Fuyi Wang²  Xiang Zhou³  Lan Jin³  Guangxiu Deng³ 

[1] Beijing 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, China;College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, China;National Glycoengineering Research Center, Shandong Key Laboratory of Carbohydrate Chemistry and Glycobiology, Shandong University, Qingdao, China;

关键词: heparin;    β-amyloid peptide;    interaction;    NMR;    hydrogen/deuterium exchange mass spectrometry;   

DOI  :  10.3389/fmolb.2022.824146

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown