Figure 1.

The chemical structure and dose–response curve of Aβ–fibrinogen interaction inhibitors. (A) TAMRA–labeled Aβ peptide was bound to fibrinogen and the test compound, and the anisotropy of TAMRA–Aβ–fibrinogen binding was determined by FP. (B) Biotin-labeled Aβ42, which binds a streptavidin donor, was incubated with fibrinogen, which binds a protein A acceptor bead coated with antifibrinogen antibody. Aβ42 and fibrinogen interactions bring the beads in close proximity, resulting in the excitation of the donor beads and release of singlet oxygen molecules that triggers light emission in acceptor beads (AlphaLISA [AL]). (C) The half-maximal inhibitory concentration (IC50) values of the indicated compounds were determined by dose–response FP and AL experiments and are indicated inside the panel (red, FP; blue, AL). A quenching test was also performed to calculate how much each hit compound interfered with the AL signal at 10 µM concentration. Quenching values are indicated below the dose–response curve. n = 3–4 repeats per assay and all error bars indicate SEM. Data are representative of at least three independent experiments.

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