Development of photocrosslinked sialic acid containing polymers for use in Aβ toxicity attenuation

beta-Amyloid peptide (A beta), the primary protein component in senile plaques associated with Alzheimer's disease (AD), has been implicated in neurotoxicity associated with AD. Previous studies have shown that the A beta-neuronal membrane interaction plays a crucial role in A beta toxicity. More specifically, it is thought that A beta interacts with ganglioside rich and sialic acid rich regions of cell surfaces. In light of such evidence, we have hypothesized that the A beta-membrane sialic acid interaction could be inhibited through use of a biomimic multivalent sialic acid compound that would compete with the cell surface for A beta binding. To explore this hypothesis, we synthesized a series of photocrosslinked sialic acid containing oligosaccharides and tested their ability to bind A beta and attenuate A beta toxicity in cell culture assays. We show that a polymer prepared via the photocrosslinking of disialyllacto-N-tetraose (DSLNT) was able to attenuate A beta toxicity at low micromolar concentrations without adversely affecting the cell viability. Polymers prepared from mono-sialyl-oligosaccharides were less effective at A beta toxicity attenuation. These results demonstrate the feasibility of using photocrosslinked sialyl-oligosaccharides for prevention of A beta toxicity in vitro and may provide insight into the design of new materials for use in attenuation of A beta toxicity associated with AD. (c) 2008 Elsevier Ltd. All rights reserved.