ABSTRACT: A new family of fluorescent markers containing an amino naphthalenyl-2-cyano-acrylate (ANCA) motif has been synthesized and evaluated for its capability to associate with aggregated β-amyloid (Aβ) peptides. These fluorescent probes contain a nitrogen donor group that is connected via a naphthalene unit to an electron acceptor motif containing water solubilizing groups (WSGs). Chemical modifications were intro- duced to explore their effect on the capability of theANCA-based probes to fluorescently label aggregated Aβ peptides. All synthesized probes bind to aggregated Aβ fibrils with low micromolar affinity and fluorescently stain amyloid deposits in human brain tissue from patients with Alzheimers disease.We found that structural modifications of the WSG site do not affect considerably the binding affinity. However, changes of the nitrogen donor group alter significantly the binding affinity of these probes. Also, increasing the hydrophilicity of the donor group leads to improved contrast between the Aβ deposits and the surrounding tissue in histological staining experiments.
CITATION STYLE
Chang, W. M., Dakanali, M., Capule, C. C., Sigurdson, C. J., Yang, J., & Theodorakis, E. a. (2011). Plaques in Human Tissue. ACS Chemical Neuroscience, 2(5), 249–255. Retrieved from http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3129977&tool=pmcentrez&rendertype=abstract
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