Probing Amyloid β Interactions with Synthetic Heparan Sulfate Oligosaccharides

Peng Wang, Jing Zhao, Seyedmehdi Hossaini Nasr, Sarah A. Otieno, Fuming Zhang, Wei Qiang, Robert J. Linhardt, Xuefei Huang

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

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.

Original languageEnglish
Pages (from-to)1894-1899
Number of pages6
JournalACS Chemical Biology
Volume16
Issue number10
DOIs
StatePublished - 15 Oct 2021
Externally publishedYes

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