title: An Iridium(III) Complex as a Photoactivatable Tool for Oxidation of Amyloidogenic Peptides with Subsequent Modulation of Peptide Aggregation.
abstract: 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 IrIIIcenter 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.
authors.affiliation: Department of Chemistry, Ulsan National Institute of Science and Technology (UNIST), Ulsan, 44919, Republic of Korea.
authors.forename: Juhye
authors.initials: J
authors.lastname: Kang
authors.affiliation: Department of Chemistry, Ulsan National Institute of Science and Technology (UNIST), Ulsan, 44919, Republic of Korea.
authors.forename: Shin Jung C
authors.initials: SJ
authors.lastname: Lee
authors.affiliation: Department of Chemistry, Ulsan National Institute of Science and Technology (UNIST), Ulsan, 44919, Republic of Korea.
authors.forename: Jung Seung
authors.initials: JS
authors.lastname: Nam
authors.affiliation: School of Life Sciences, UNIST, Ulsan, 44919, Republic of Korea.
authors.forename: Hyuck Jin
authors.initials: HJ
authors.lastname: Lee
authors.affiliation: Department of Chemistry, Ulsan National Institute of Science and Technology (UNIST), Ulsan, 44919, Republic of Korea.
authors.forename: Myeong-Gyun
authors.initials: MG
authors.lastname: Kang
authors.affiliation: Department of Chemistry, University of Michigan, Ann Arbor, MI, 48109, USA.
authors.forename: Kyle J
authors.initials: KJ
authors.lastname: Korshavn
authors.affiliation: Department of Chemistry, Ulsan National Institute of Science and Technology (UNIST), Ulsan, 44919, Republic of Korea.
authors.forename: Hyun-Tak
authors.initials: HT
authors.lastname: Kim
authors.affiliation: Department of Emerging Materials Science, Daegu Gyeongbuk Institute of Science and Technology (DGIST), Daegu, 42988, Republic of Korea.
authors.forename: Jaeheung
authors.initials: J
authors.lastname: Cho
authors.affiliation: Department of Chemistry, University of Michigan, Ann Arbor, MI, 48109, USA.|Biophysics, University of Michigan, Ann Arbor, MI, 48109, USA.
authors.forename: Ayyalusamy
authors.initials: A
authors.lastname: Ramamoorthy
authors.affiliation: Department of Chemistry, Ulsan National Institute of Science and Technology (UNIST), Ulsan, 44919, Republic of Korea.
authors.forename: Hyun-Woo
authors.initials: HW
authors.lastname: Rhee
authors.affiliation: Department of Chemistry, Ulsan National Institute of Science and Technology (UNIST), Ulsan, 44919, Republic of Korea.
authors.forename: Tae-Hyuk
authors.initials: TH
authors.lastname: Kwon
authors.affiliation: Department of Chemistry, Ulsan National Institute of Science and Technology (UNIST), Ulsan, 44919, Republic of Korea.
authors.forename: Mi Hee
authors.identifier: http://orcid.org/0000-0003-3377-4996
authors.initials: MH
authors.lastname: Lim
mesh_terms: D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000378:metabolism; D056831:Coordination Complexes / Q000737:chemistry*; D006801:Humans; D007495:Iridium / Q000737:chemistry*; D058228:Islet Amyloid Polypeptide / Q000737:chemistry / Q000378:metabolism; D008027:Light; D010084:Oxidation-Reduction; D066329:Protein Aggregates / Q000528:radiation effects; D021241:Spectrometry, Mass, Electrospray Ionization; D051844:alpha-Synuclein / Q000737:chemistry / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D056831:Coordination Complexes; D058228:Islet Amyloid Polypeptide; D066329:Protein Aggregates; D051844:alpha-Synuclein; D007495:Iridium
keywords: aggregation; iridium; oxidation; peptides; photochemistry