title: Hybrid peptides attenuate cytotoxicity of beta-amyloid by inhibiting its oligomerization: implication from solvent effects.
abstract: Abnormal assembly of monomeric beta-amyloid (Abeta) 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 Abeta recognition motif and the solvent disruptive sequences. We found that in vitro all synthetic peptides with the recognition motif can affect Abeta fibrillization and alter the morphology of Abeta aggregates variously, different from those without the recognition motif. The effects of peptides containing recognition motif on Abeta 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 Abeta in cell culture probably by decreasing the amount of toxic Abeta oligomers. These results indicate that recognition domain and solvent effect should be considered as important factors when designing molecules to target Abeta aggregation.
authors.affiliation: Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University, Beijing 100084, China.
authors.forename: Xun
authors.initials: X
authors.lastname: Sun
authors.forename: Wei-hui
authors.initials: WH
authors.lastname: Wu
authors.forename: Qian
authors.initials: Q
authors.lastname: Liu
authors.forename: Mei-sha
authors.initials: MS
authors.lastname: Chen
authors.forename: Ye-ping
authors.initials: YP
authors.lastname: Yu
authors.forename: Ying
authors.initials: Y
authors.lastname: Ma
authors.forename: Yu-fen
authors.initials: YF
authors.lastname: Zhao
authors.forename: Yan-mei
authors.initials: YM
authors.lastname: Li
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000378:metabolism / Q000633:toxicity* / Q000648:ultrastructure; D000818:Animals; D045744:Cell Line, Tumor; D051379:Mice; D046529:Microscopy, Electron, Transmission; D008969:Molecular Sequence Data; D009474:Neurons / Q000187:drug effects*; D010455:Peptides / Q000737:chemistry* / Q000494:pharmacology*; D055503:Protein Multimerization / Q000187:drug effects*
chemical_list: D016229:Amyloid beta-Peptides; D010455:Peptides