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Probing Amyloid β Interactions with Synthetic Heparan Sulfate Oligosaccharides.


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.

SUBMITTER: Wang P 

PROVIDER: S-EPMC8444215 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature

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Probing Amyloid β Interactions with Synthetic Heparan Sulfate Oligosaccharides.

Wang Peng P   Zhao Jing J   Hossaini Nasr Seyedmehdi S   Otieno Sarah A SA   Zhang Fuming F   Qiang Wei W   Linhardt Robert J RJ   Huang Xuefei X  

ACS chemical biology 20210216 10


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-<i>O</i>, 6-<i>O</i>, and <i>N</i>-sulfations exhibited the st  ...[more]

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