School of Chemistry, ‡Bio21 Molecular Science and Biotechnology Institute, §Florey Institute of Neuroscience and Mental Health, □Department of Pharmacology, and ∥Department of Pathology, University of Melbourne, Parkville , Melbourne, Victoria, 3010, Australia.
J Am Chem Soc. 2013 Oct 30;135(43):16120-32. doi: 10.1021/ja4057807. Epub 2013 Oct 16.
One of the pathological hallmarks of Alzheimer's disease is the presence of amyloid-β plaques in the brain and the major constituent of these plaques is aggregated amyloid-β peptide. New thiosemicarbazone-pyridylhydrazine based ligands that incorporate functional groups designed to bind amyloid-β plaques have been synthesized. The new ligands form stable four coordinate complexes with a positron-emitting radioactive isotope of copper, (64)Cu. Two of the new Cu(II) complexes include a functionalized styrylpyridine group and these complexes bind to amyloid-β plaques in samples of post-mortem human brain tissue. Strategies to increase brain uptake by functional group manipulation have led to a (64)Cu 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-β plaques.
阿尔茨海默病的病理特征之一是大脑中存在淀粉样β斑块，这些斑块的主要成分是聚集的淀粉样β肽。已经合成了新的基于硫代缩氨基脲-吡啶基腙的配体，这些配体包含设计用于结合淀粉样β斑块的官能团。新的配体与正电子发射放射性同位素铜（64Cu）形成稳定的四配位络合物。两个新的 Cu(II)配合物包含官能化的苯乙烯吡啶基团，并且这些配合物与死后人脑组织样本中的淀粉样β斑块结合。通过官能团修饰来增加脑摄取的策略导致了一种能够有效穿过野生型小鼠血脑屏障的（64）Cu 配合物。本文描述的新配合物为将金属配合物递送至淀粉样β斑块提供了思路。
