期刊
CHEMISTRY-A EUROPEAN JOURNAL
卷 23, 期 7, 页码 1645-1653出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/chem.201604751
关键词
aggregation; iridium; oxidation; peptides; photochemistry
资金
- UNIST research fund [1.160001.01]
- National Research Foundation of Korea (NRF) Grant-Korean Government [NRF-2014S1A2A2028270, NRF2014R1A2A2A01004877, NRF-2016R1A5A1009405]
- National Institutes of Health (NIH)
- Ministry of Science, ICT and Future Planning [KCRC 2014M1A8A1049320]
- Global Ph.D. fellowship program through the National Research Foundation of Korea (NRF)-Ministry of Education [NRF-2015HIA2A1030823]
- University of Michigan Protein Folding Disease Initiative
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 bio-physical investigations illuminate that the oxidation of representative amyloidogenic peptides (i.e., amyloid-beta, alpha-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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据