title: para-Sulfonatocalix[n]arenes Inhibit Amyloid β-Peptide Fibrillation and Reduce Amyloid Cytotoxicity.
abstract: Amyloid β-peptide (Aβ) fibrillation is a major hallmark of Alzheimer's disease (AD). Inhibition of Aβ fibrillation is thus considered to be an effective strategy for AD prevention and treatment. Here we show that para-sulfonatocalix[n]arenes (SC[n]A, n=4, 6, 8), a class of amphiphilic calixarene derivatives, can bind to Aβ42through nonspecific and multipoint hydrophobic interactions. Their binding leads to a pronounced delay in β-sheet adoption and formation of multiple secondary structures of the peptide, accompanied by changes at the level of the fibrillary architecture. Furthermore, the ζ-potential value of Aβ42incubated with SC[6/8]A decreased, which correlated with the reduction of amyloid cytotoxicity. Overall, the SC[n]A effectively inhibits Aβ42fibrillation and reduces amyloid cytotoxicity, and SC[8]A showed the best performance among the three macrocycles, possibly owing to its having the strongest interactions with Aβ42.
authors.affiliation: Department of Biochemical Engineering and Key Laboratory of Systems Bioengineering, Ministry of Education, School of Chemical Engineering and Technology, Tianjin University, Tianjin, 300354, P.R. China.
authors.forename: Ziyuan
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Biochemical Engineering and Key Laboratory of Systems Bioengineering, Ministry of Education, School of Chemical Engineering and Technology, Tianjin University, Tianjin, 300354, P.R. China.
authors.forename: Shipeng
authors.initials: S
authors.lastname: Tao
authors.affiliation: Department of Biochemical Engineering and Key Laboratory of Systems Bioengineering, Ministry of Education, School of Chemical Engineering and Technology, Tianjin University, Tianjin, 300354, P.R. China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Dong
authors.affiliation: Department of Biochemical Engineering and Key Laboratory of Systems Bioengineering, Ministry of Education, School of Chemical Engineering and Technology, Tianjin University, Tianjin, 300354, P.R. China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Sun
mesh_terms: D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000633:toxicity; D047250:Calixarenes / Q000737:chemistry* / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D002942:Circular Dichroism; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D046529:Microscopy, Electron, Transmission; D013451:Sulfonic Acids / Q000737:chemistry* / Q000494:pharmacology; D013816:Thermodynamics
chemical_list: D016229:Amyloid beta-Peptides; D013451:Sulfonic Acids; D047250:Calixarenes
keywords: Alzheimer's disease; aggregation; inhibitors; macrocycles; peptides