Inhibitors of Fibril Formation and Cytotoxicity of β-Amyloid Peptide Composed of KLVFF Recognition Element and Flexible Hydrophilic Disrupting Element

• Published in: Biochemical and biophysical research communications Vol. 290; no. 1; pp. 121 - 124
• Main Authors: Watanabe, Ken-ichi, Nakamura, Kazuhiko, Akikusa, Shingo, Okada, Tomoko, Kodaka, Masato, Konakahara, Takeo, Okuno, Hiroaki
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 11.01.2002
• Subjects: Amyloid beta-Peptides - chemistry; Amyloid beta-Peptides - toxicity; Cell Division - drug effects; Cell Survival - drug effects; Coloring Agents - pharmacology; Congo Red - pharmacology; Enzyme Inhibitors - pharmacology; Fluorescent Dyes - pharmacology; Humans; Models, Chemical; Peptide Fragments - chemistry; Peptide Fragments - toxicity; Peptides - chemistry; Pigments, Biological - pharmacology; Protein Binding; Protein Structure, Tertiary; Tetrazolium Salts - pharmacology; Thiazoles - pharmacology; Time Factors; Tumor Cells, Cultured
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1006/bbrc.2001.6191

β-Amyloid peptide (Aβ) is the main protein components of neuritic plaques and its neurotoxicity would be exposed by formation of aggregate. The aggregation inhibitors composed of an Aβ recognition element (KLVFF) and a flexible hydrophilic disrupting element (aminoethoxy ethoxy acetate and aspartate) are designed and chemically synthesized. The inhibitory effects are examined by a pigment binding assay using Congo red or thioflavin T. The present compounds suppress the formation of aggregate, and the compound DDX3 is an especially effective inhibitor. In addition, the synthesized compounds efficiently suppress the cytotoxicity of Aβ against IMR-32 neuroblastoma cells in vitro.