In:
Chemistry – A European Journal, Wiley, Vol. 23, No. 7 ( 2017-01-31), p. 1645-1653
Kurzfassung:
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.
Materialart:
Online-Ressource
ISSN:
0947-6539
,
1521-3765
DOI:
10.1002/chem.201604751
Sprache:
Englisch
Verlag:
Wiley
Publikationsdatum:
2017
ZDB Id:
1478547-X
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