期刊
CHEMISTRY-A EUROPEAN JOURNAL
卷 27, 期 5, 页码 1777-1786出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/chem.202003949
关键词
amyloid beta-peptides; bioinorganic chemistry; chelates; copper; reactive oxygen species
资金
- ERC aLzINK [638712]
- PRESTIGE Programm [PCOFUND-GA-2013-609102]
- European Research Council (ERC) [638712] Funding Source: European Research Council (ERC)
The study found that N-truncated peptides of Aβ are able to produce ROS in the presence of Cu-I, although to a lesser extent compared to unmodified peptides, and they are unable to fully prevent Cu(Aβ(1-16))-induced ROS production as competitor ligands.
In vitro Cu(A beta(1-x))-induced ROS production has been extensively studied. Conversely, the ability of N-truncated isoforms of A beta to alter the Cu-induced ROS production has been overlooked, even though they are main constituents of amyloid plaques found in the human brain. N-Truncated peptides at the positions 4 and 11 (A beta(4-x) and A beta(11-x)) contain an amino-terminal copper and nickel (ATCUN) binding motif (H2N-Xxx-Zzz-His) that confer them different coordination sites and higher affinities for Cu-II compared to the A beta(1-x) peptide. It has further been proposed that the role of A beta(4-x) peptide is to quench Cu-II toxicity in the brain. However, the role of Cu-I coordination has not been investigated to date. In contrast to Cu-II, Cu-I coordination is expected to be the same for N-truncated and N-intact peptides. Herein, we report in-depth characterizations and ROS production studies of Cu (Cu-I and Cu-II) complexes of the A beta(4-16) and A beta(11-16) N-truncated peptides. Our findings show that the N-truncated peptides do produce ROS when Cu-I is present in the medium, albeit to a lesser extent than the unmodified counterpart. In addition, when used as competitor ligands (i.e., in the presence of A beta(1-16)), the N-truncated peptides are not able to fully preclude Cu(A beta(1-16))-induced ROS production.
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