Chemical strategies to modify amyloidogenic peptides using iridium(iii) complexes: coordination and photo-induced oxidation

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Amyloidogenic peptides are considered central pathological contributors towards neurodegeneration as observed in neurodegenerative disorders [e.g., amyloid-beta (A beta) peptides in Alzheimer's disease (AD)]; however, their roles in the pathologies of such diseases have not been fully elucidated since they are challenging targets to be studied due to their heterogeneous nature and intrinsically disordered structure. Chemical approaches to modify amyloidogenic peptides would be valuable in advancing our molecular-level understanding of their involvement in neurodegeneration. Herein, we report effective chemical strategies for modification of A beta peptides (i.e., coordination and coordination-/photo-mediated oxidation) implemented by a single Ir(iii) complex in a photo-dependent manner. Such peptide variations can be achieved by our rationally designed Ir(iii) complexes (Ir-Me, Ir-H, Ir-F, and Ir-F2) leading to significantly modulating the aggregation pathways of two main A beta isoforms, A beta(40) and A beta(42), as well as the production of toxic A beta species. Overall, we demonstrate chemical tactics for modification of amyloidogenic peptides in an effective and manageable manner utilizing the coordination capacities and photophysical properties of transition metal complexes.
Publisher
ROYAL SOC CHEMISTRY
Issue Date
2019-07
Language
English
Article Type
Article
Citation

CHEMICAL SCIENCE, v.10, no.28, pp.6855 - 6862

ISSN
2041-6520
DOI
10.1039/c9sc00931k
URI
http://hdl.handle.net/10203/264208
Appears in Collection
CH-Journal Papers(저널논문)
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