Research Article
Hybrid peptides attenuate cytotoxicity of β-amyloid by inhibiting its oligomerization: Implication from solvent effects

Xun Sun, Wei-hui Wu, Qian Liu, Mei-sha Chen, Ye-ping Yu, Ying Ma, Yu-fen Zhao and Yan-mei Li

Peptides, 2009, 30(7), 1282-1287. DOI: 10.1016/j.peptides.2009.04.012

Abstract

Abnormal assembly of monomeric β-amyloid (Aβ) in Alzheimer's disease leads to the formation of most neurotoxic oligomers in vivo. In this study, we explored a linking strategy to design hybrid peptides, by combining the Aβ recognition motif and the solvent disruptive sequences. We found that in vitro all synthetic peptides with the recognition motif can affect Aβ fibrillization and alter the morphology of Aβ aggregates variously, different from those without the recognition motif. The effects of peptides containing recognition motif on Aβ aggregation correlate with their abilities to change the surface tension of solutions. In addition, compounds with the recognition motif, not those without such motif, can inhibit cytotoxicity of Aβ in cell culture probably by decreasing the amount of toxic Aβ oligomers. These results indicate that recognition domain and solvent effect should be considered as important factors when designing molecules to target Aβ aggregation.

ASCI-ID: 744-42