Inhibition of [beta]-amyloid peptide self-assembly and cytotoxicity by poly(LVFF-co-[beta]-amino ester)

The [beta]-amyloid (A[beta]) peptide plays an important role in the onset and progress of Alzheimer's disease (AD). Therefore, studies on inhibiting fibril formation and thus neurotoxicity of A[beta] could be beneficial for the prevention and treatment of AD. We report a convenient synthetic approach for one-pot preparation of poly-([beta]-amino ester) copolymerized with the GGLVFF peptide, which is based on the frequently used inhibitor LVFF. The copolymer was found to efficiently inhibit the aggregation and fibrillation of A[beta]42 by using fluorescence assay and atomic force microscopy. Reduced [beta]-sheet formation of A[beta]42 peptide after addition of copolymer was observed by circular dichroism. Furthermore, the cell viability assay confirmed that the toxicity of A[beta]42 for SH-SY5Y cells was markedly reduced in the presence of copolymer. This could be beneficial for AD prevention and treatment and also for the molecular design of inhibitory agents for other amyloidoses. Copyright © 2015 European Peptide Society and John Wiley & Sons, Ltd.