title: Spectroscopic study on the interaction of Aβ42 with di(picolyl)amine derivatives and the toxicity to SH-S5Y5 cells.
abstract: In order to confirm the neurotoxicity of bifunctional chelators containing hydrophobic groups and metal chelating moiety, the interaction of di(picolyl)amine (dpa) derivatives toward Aβ42 peptide was investigated. Fluorescence titration reveals that a hydrophobic chelator (such as BODIPY) shows high binding affinity to amyloid Aβ42. Circular dichroism (CD) spectra confirm that the hydrophobic bifunctional chelator can decrease α-helix fraction and increase the β-sheet fraction of amyloid Aβ42. In particular, experimental results indicate that a bifunctional chelator can assemble with Cu(II)-Aβ42 forming chelator-Cu(II)-Aβ42 nanospheres, which are toxic to SH-S5Y5 cells. The hydrophobic interaction between the chelator and the amyloid peptide (Aβ42) has great contribution to the formation of neurotoxic chelator-Cu(II)-Aβ42 nanospheres. This work gives a general guide to the development of low cytotoxic inhibitors of Aβ42 aggregation.
authors.affiliation: School of Chemistry and Chemical Engineering, Jiangsu University, Zhenjiang 212013, PR China.
authors.forename: Meng-Yun
authors.initials: MY
authors.lastname: Kong
authors.affiliation: School of Chemistry and Chemical Engineering, Jiangsu University, Zhenjiang 212013, PR China. Electronic address: chenqy@ujs.edu.cn.
authors.forename: Qiu-Yun
authors.initials: QY
authors.lastname: Chen
authors.affiliation: School of Chemistry and Chemical Engineering, Jiangsu University, Zhenjiang 212013, PR China.
authors.forename: Ling
authors.initials: L
authors.lastname: Yao
authors.affiliation: School of Chemistry and Chemical Engineering, Jiangsu University, Zhenjiang 212013, PR China.
authors.forename: Yin-Bing
authors.initials: YB
authors.lastname: Wang
mesh_terms: D000544:Alzheimer Disease; D016229:Amyloid beta-Peptides / Q000737:chemistry*; D045744:Cell Line, Tumor; D002614:Chelating Agents / Q000737:chemistry; D002942:Circular Dichroism; D003300:Copper / Q000737:chemistry; D006801:Humans; D046529:Microscopy, Electron, Transmission; D010446:Peptide Fragments / Q000737:chemistry*; D017433:Protein Structure, Secondary; D013050:Spectrometry, Fluorescence; D013057:Spectrum Analysis; D015032:Zinc / Q000737:chemistry
chemical_list: D016229:Amyloid beta-Peptides; D002614:Chelating Agents; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D003300:Copper; D015032:Zinc
keywords: Amyloid peptide; BODIPY; Chelator; Cytotoxic; Inhibitor