TY - JOUR
T1 - Probing Amyloid β Interactions with Synthetic Heparan Sulfate Oligosaccharides
AU - Wang, Peng
AU - Zhao, Jing
AU - Hossaini Nasr, Seyedmehdi
AU - Otieno, Sarah A.
AU - Zhang, Fuming
AU - Qiang, Wei
AU - Linhardt, Robert J.
AU - Huang, Xuefei
N1 - Publisher Copyright:
© 2021 American Chemical Society.
PY - 2021/10/15
Y1 - 2021/10/15
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85101810563&partnerID=8YFLogxK
U2 - 10.1021/acschembio.0c00904
DO - 10.1021/acschembio.0c00904
M3 - Article
C2 - 33592143
AN - SCOPUS:85101810563
SN - 1554-8929
VL - 16
SP - 1894
EP - 1899
JO - ACS Chemical Biology
JF - ACS Chemical Biology
IS - 10
ER -