title: Study of a Bifunctional Aβ Aggregation Inhibitor with the Abilities of Antiamyloid-β and Copper Chelation.
abstract: In this study, a bifunctional Aβ aggregation inhibitor peptide, GGHRYYAAFFARR (GR), with the abilities to bind copper and antiamyloid was designed to inhibit the neurotoxicity of the Aβ-Cu(II) complex. The thioflavin T (ThT) assay, turbidimetric analysis, transmission electron microscopy (TEM), and (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) (MTT) assay were used to study its potential inhibitory effect on Aβ aggregation. Our findings indicate that GGH was the specific chelating sequence and that the RYYAAFFARR (RR) component acted as an aggregation inhibitor. More importantly, GR significantly decreased the cytotoxicity of the Aβ-Cu(II) complex. The cell viability improved to 88%, which was higher than with the single functional peptide GGH and RR by 39% and 20%, respectively. Moreover, the qualitative effect of Cu(II) on the Aβ-Cu(II) complex was also studied. Our results indicate that Cu(II) induces the formation of the β-sheet structure with a subequimolar Cu(II):Aβ molar ratio (0.25:1) but led to increased ROS production at a supra-equimolar ratio.
authors.affiliation: Key Laboratory of Functional Polymer Materials of Ministry of Education, Institute of Polymer Chemistry, and ‡Collaborative Innovation Center of Chemical Science and Engineering, Nankai University , Tianjin 300071, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Functional Polymer Materials of Ministry of Education, Institute of Polymer Chemistry, and ‡Collaborative Innovation Center of Chemical Science and Engineering, Nankai University , Tianjin 300071, China.
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Hu
authors.affiliation: Key Laboratory of Functional Polymer Materials of Ministry of Education, Institute of Polymer Chemistry, and ‡Collaborative Innovation Center of Chemical Science and Engineering, Nankai University , Tianjin 300071, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Key Laboratory of Functional Polymer Materials of Ministry of Education, Institute of Polymer Chemistry, and ‡Collaborative Innovation Center of Chemical Science and Engineering, Nankai University , Tianjin 300071, China.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Yuan
mesh_terms: D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000378:metabolism; D000818:Animals; D002614:Chelating Agents / Q000737:chemistry* / Q000494:pharmacology; D003300:Copper / Q000737:chemistry; D004353:Drug Evaluation, Preclinical; D008969:Molecular Sequence Data; D016716:PC12 Cells; D010455:Peptides / Q000737:chemistry* / Q000494:pharmacology; D066263:Protein Aggregation, Pathological / Q000517:prevention & control*; D051381:Rats
chemical_list: D016229:Amyloid beta-Peptides; D002614:Chelating Agents; D010455:Peptides; D003300:Copper