Probing Amyloid β Interactions with Synthetic Heparan Sulfate Oligosaccharides

Heparan sulfate (HS) can play important roles in the biology and pathology of amyloid beta (A beta), a hallmark of Alzheimer's disease. To better understand the structure-activity relationship of HS/A beta interactions, synthetic HS oligosaccharides ranging from tetrasaccharides to decasaccharides have been utilized to study A beta 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 A beta among the tetrasaccharides investigated. Elongating the glycan length to hexa- and deca-saccharides significantly enhanced A beta affinity compared to the corresponding HS tetrasaccharide. Solid state NMR studies of the complexes of A beta with HS hexa- and deca-saccharides showed most significant chemical shift perturbation in the C-terminus residues of A beta. The strong binding HS oligosaccharides could reduce the cellular toxicities induced by A beta. This study provides new insights into HS/A beta interactions, highlighting how synthetic structurally well-defined HS oligosaccharides can assist in biological understanding of A beta.

Automated summary

The highly sulfated HS oligosaccharides show the strongest binding affinity with A beta and can reduce cellular toxicities induced by A beta. Elongating the glycan length significantly enhances A beta affinity. This study provides new insights into HS/A beta interactions.