Probing Aβ interactions with synthetic heparan sulfate oligosaccharides
No Thumbnail Available
Authors
Wang, P.
Zhao, J.
Hossaini Nasr, S.
Otieno, S.A.
Zhang, F.
Qiang, W.
Linhardt, Robert J.
Huang, X.
Issue Date
2021
Type
Article
Language
ENG
Keywords
Biology , Chemistry and chemical biology , Chemical and biological engineering , Biomedical engineering
Alternative Title
Abstract
Heparan sulfate (HS) can play important roles in the biology and pathology of amyloid β (Aβ), a hallmark of Alzheimer's disease. To better understand the structure-activity relationship of HS/Aβ interactions, synthetic HS oligosaccharides ranging from tetrasaccharides to decasaccharides have been utilized to study Aβ interactions. Surface plasmon resonance experiments showed that the highly sulfated HS tetrasaccharides bearing full 2-O, 6-O, and N-sulfations exhibited the strongest binding with Aβ among the tetrasaccharides investigated. Elongating the glycan length to hexa- and deca-saccharides significantly enhanced Aβ affinity compared to the corresponding HS tetrasaccharide. Solid state NMR studies of the complexes of Aβ with HS hexa- and deca-saccharides showed most significant chemical shift perturbation in the C-terminus residues of Aβ. The strong binding HS oligosaccharides could reduce the cellular toxicities induced by Aβ. This study provides new insights into HS/Aβ interactions, highlighting how synthetic structurally well-defined HS oligosaccharides can assist in biological understanding of Aβ.
Description
ACS Chemical Biology, 16, 1894-1899
Note : if this item contains full text it may be a preprint, author manuscript, or a Gold OA copy that permits redistribution with a license such as CC BY. The final version is available through the publisher’s platform.
Note : if this item contains full text it may be a preprint, author manuscript, or a Gold OA copy that permits redistribution with a license such as CC BY. The final version is available through the publisher’s platform.
Full Citation
Probing Aβ interactions with synthetic heparan sulfate oligosaccharides, P. Wang, J. Zhao, S. Hossaini Nasr, S. A. Otieno, F. Zhang, W. Qiang, R. J. Linhardt, X. Huang, ACS Chemical Biology, 16, 1894-1899, 2021.