期刊
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
卷 135, 期 43, 页码 16120-16132出版社
AMER CHEMICAL SOC
DOI: 10.1021/ja4057807
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资金
- Australian Research Council
- National Health and Medical Research Council (Australia)
One of the pathological hallmarks of Alzheimer's disease is the presence of amyloid-beta plaques in the brain and the major constituent of these plaques is aggregated amyloid-beta peptide. New thiosemicarbazone-pyridylhydrazine based ligands that incorporate functional groups designed to bind amyloid-beta plaques have been synthesized. The new ligands form stable four coordinate complexes with a positron-emitting radioactive isotope of copper, Cu-64. Two of the new Cu-II complexes include a functionalized styrylpyridine group and these complexes bind to amyloid-beta plaques in samples of post-mortem human brain tissue. Strategies to increase brain uptake by functional group manipulation have led to a Cu-64 complex that effectively crosses the blood-brain barrier in wild-type mice. The new complexes described in this manuscript provide insight into strategies to deliver metal complexes to amyloid-beta plaques.
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