Inhibitors of fibril formation and cytotoxicity of beta-amyloid peptide composed of KLVFF recognition element and flexible hydrophilic disrupting element.
Beta-Amyloid peptide (Abeta) is the main protein components of neuritic plaques and its neurotoxicity would be exposed by formation of aggregate. The aggregation inhibitors composed of an Abeta 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 Abeta against IMR-32 neuroblastoma cells in vitro.
Watanabe
Ken-ichi
K
National Institute of Advanced Industrial Science and Technology (AIST), Central 6, 1-1-1 Higashi, Tsukuba, Ibaraki 305-8566, Japan.
Nakamura
Kazuhiko
K
Akikusa
Shingo
S
Okada
Tomoko
T
Kodaka
Masato
M
Konakahara
Takeo
T
Okuno
Hiroaki
H
D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000633:toxicity*; D052160:Benzothiazoles; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004396:Coloring Agents / Q000494:pharmacology; D003224:Congo Red / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005456:Fluorescent Dyes / Q000494:pharmacology; D006801:Humans; D008956:Models, Chemical; D010446:Peptide Fragments / Q000737:chemistry* / Q000633:toxicity*; D010455:Peptides / Q000737:chemistry; D010860:Pigments, Biological / Q000494:pharmacology; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D013778:Tetrazolium Salts / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology; D013997:Time Factors; D014407:Tumor Cells, Cultured
D016229:Amyloid beta-Peptides; D052160:Benzothiazoles; D004396:Coloring Agents; D004791:Enzyme Inhibitors; D005456:Fluorescent Dyes; D010446:Peptide Fragments; D010455:Peptides; D010860:Pigments, Biological; D013778:Tetrazolium Salts; D013844:Thiazoles; C442220:amyloid beta-protein (2-42); C009462:thioflavin T; D003224:Congo Red; C022616:thiazolyl blue