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

Amyloidogenic peptides are considered central pathological contributors towards neurodegeneration as observed in neurodegenerative disorders [e.g., amyloid-β (Aβ) peptides in Alzheimer's disease (AD)]; however, their roles in the pathologies of such diseases have not been fully elucidated since...

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Autores principales: Kang, Juhye, Nam, Jung Seung, Lee, Hyuck Jin, Nam, Geewoo, Rhee, Hyun-Woo, Kwon, Tae-Hyuk, Lim, Mi Hee
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Royal Society of Chemistry 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6657414/
https://www.ncbi.nlm.nih.gov/pubmed/31391908
http://dx.doi.org/10.1039/c9sc00931k
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author Kang, Juhye
Nam, Jung Seung
Lee, Hyuck Jin
Nam, Geewoo
Rhee, Hyun-Woo
Kwon, Tae-Hyuk
Lim, Mi Hee
author_facet Kang, Juhye
Nam, Jung Seung
Lee, Hyuck Jin
Nam, Geewoo
Rhee, Hyun-Woo
Kwon, Tae-Hyuk
Lim, Mi Hee
author_sort Kang, Juhye
collection PubMed
description Amyloidogenic peptides are considered central pathological contributors towards neurodegeneration as observed in neurodegenerative disorders [e.g., amyloid-β (Aβ) 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 Aβ 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 Aβ isoforms, Aβ(40) and Aβ(42), as well as the production of toxic Aβ 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.
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spelling pubmed-66574142019-08-07 Chemical strategies to modify amyloidogenic peptides using iridium(iii) complexes: coordination and photo-induced oxidation Kang, Juhye Nam, Jung Seung Lee, Hyuck Jin Nam, Geewoo Rhee, Hyun-Woo Kwon, Tae-Hyuk Lim, Mi Hee Chem Sci Chemistry Amyloidogenic peptides are considered central pathological contributors towards neurodegeneration as observed in neurodegenerative disorders [e.g., amyloid-β (Aβ) 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 Aβ 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 Aβ isoforms, Aβ(40) and Aβ(42), as well as the production of toxic Aβ 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. Royal Society of Chemistry 2019-06-05 /pmc/articles/PMC6657414/ /pubmed/31391908 http://dx.doi.org/10.1039/c9sc00931k Text en This journal is © The Royal Society of Chemistry 2019 http://creativecommons.org/licenses/by/3.0/ This article is freely available. This article is licensed under a Creative Commons Attribution 3.0 Unported Licence (CC BY 3.0)
spellingShingle Chemistry
Kang, Juhye
Nam, Jung Seung
Lee, Hyuck Jin
Nam, Geewoo
Rhee, Hyun-Woo
Kwon, Tae-Hyuk
Lim, Mi Hee
Chemical strategies to modify amyloidogenic peptides using iridium(iii) complexes: coordination and photo-induced oxidation
title Chemical strategies to modify amyloidogenic peptides using iridium(iii) complexes: coordination and photo-induced oxidation
title_full Chemical strategies to modify amyloidogenic peptides using iridium(iii) complexes: coordination and photo-induced oxidation
title_fullStr Chemical strategies to modify amyloidogenic peptides using iridium(iii) complexes: coordination and photo-induced oxidation
title_full_unstemmed Chemical strategies to modify amyloidogenic peptides using iridium(iii) complexes: coordination and photo-induced oxidation
title_short Chemical strategies to modify amyloidogenic peptides using iridium(iii) complexes: coordination and photo-induced oxidation
title_sort chemical strategies to modify amyloidogenic peptides using iridium(iii) complexes: coordination and photo-induced oxidation
topic Chemistry
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6657414/
https://www.ncbi.nlm.nih.gov/pubmed/31391908
http://dx.doi.org/10.1039/c9sc00931k
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