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An Iridium(III) Complex as a Photoactivatable Tool for Oxidation of Amyloidogenic Peptides with Subsequent Modulation of Peptide Aggregation
Author(s) -
Kang Juhye,
Lee Shin Jung C.,
Nam Jung Seung,
Lee Hyuck Jin,
Kang MyeongGyun,
Korshavn Kyle J.,
Kim HyunTak,
Cho Jaeheung,
Ramamoorthy Ayyalusamy,
Rhee HyunWoo,
Kwon TaeHyuk,
Lim Mi Hee
Publication year - 2017
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201604751
Subject(s) - chemistry , peptide , iridium , amylin , amyloid (mycology) , histidine , tyrosine , protein aggregation , biochemistry , ligand (biochemistry) , biophysics , combinatorial chemistry , amino acid , receptor , biology , inorganic chemistry , islet , insulin , endocrinology , catalysis
Aggregates of amyloidogenic peptides are involved in the pathogenesis of several degenerative disorders. Herein, an iridium(III) complex, Ir‐1 , is reported as a chemical tool for oxidizing amyloidogenic peptides upon photoactivation and subsequently modulating their aggregation pathways. Ir‐1 was rationally designed based on multiple characteristics, including 1) photoproperties leading to excitation by low‐energy radiation; 2) generation of reactive oxygen species responsible for peptide oxidation upon photoactivation under mild conditions; and 3) relatively easy incorporation of a ligand on the Ir III center for specific interactions with amyloidogenic peptides. Biochemical and biophysical investigations illuminate that the oxidation of representative amyloidogenic peptides (i.e., amyloid‐β, α‐synuclein, and human islet amyloid polypeptide) is promoted by light‐activated Ir‐1 , which alters the conformations and aggregation pathways of the peptides. Additionally, their potential oxidation sites are identified as methionine, histidine, or tyrosine residues. Overall, our studies on Ir‐1 demonstrate the feasibility of devising metal complexes as chemical tools suitable for elucidating the nature of amyloidogenic peptides at the molecular level, as well as controlling their aggregation.