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• W2783158545 abstract "Abstract Dysfunctional accumulation of amyloid β‐protein (Aβ) mediated by Cu 2+ exhibits higher neurotoxicity and accelerates the progress of Alzheimer's disease, so inhibition of Cu 2+ ‐mediated Aβ aggregation and cytotoxicity has been considered as a therapeutic strategy for the disease. Herein, a nonapeptide was designed by linking HH to the C‐terminus of a peptide inhibitor of Aβ aggregation, LVFFARK (LK7). We found that the nonapeptide, LK7‐HH, possessed dual functionality, including enhanced inhibition capability on Aβ aggregation as compared to LK7, and chelating Cu 2+ with a dissociation constant of 5.50 μM. This enabled LK7‐HH to arrest the generation of reactive oxygen species catalyzed by Cu 2+ or Cu 2+ ‐Aβ complex, and to inhibit Cu 2+ ‐induced Aβ aggregation. Moreover, in contrast with the cytotoxicity of LK7 aggregates, LK7‐HH was biocompatible because HH conjugation made its aggregation behavior different from LK7. Thus, LK7‐HH efficiently suppressed Cu 2+ ‐mediated Aβ aggregation and cytotoxicity. An equimolar concentration of LK7‐HH increased cell viability from 50% to 90% when treating Aβ 40 ‐Cu 2+ complexes. The results provided insights into the roles of HH in enhancing the inhibition of Aβ and Cu 2+ ‐induced Aβ aggregations, in eliminating Cu 2+ ‐induced cytotoxicities by arresting generation of reactive oxygen species, and in making the peptide biocompatible. Therefore, this work would contribute to the design of potent peptide‐based inhibitors of Cu 2+ ‐mediated Aβ aggregation and cytotoxicity." @default.
• W2783158545 created "2018-01-26" @default.
• W2783158545 creator A5020042453 @default.
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• W2783158545 date "2018-01-10" @default.
• W2783158545 modified "2023-10-14" @default.
• W2783158545 title "Design of nonapeptide LVFFARKHH: A bifunctional agent against Cu²⁺ -mediated amyloid β-protein aggregation and cytotoxicity" @default.
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• W2783158545 doi "https://doi.org/10.1002/jmr.2697" @default.
• W2783158545 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/29318655" @default.
• W2783158545 hasPublicationYear "2018" @default.
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