Deep Red Blinking Fluorophore for Nanoscopic Imaging and Inhibition of β-Amyloid Peptide Fibrillation.

Deposition and aggregation of β-amyloid (Aβ) peptides are demonstrated to be closely related to the pathogenesis of Alzheimer's disease (AD). Development of functional molecules capable of visualizing Aβ aggregates with nanoscale resolution and even modulating Aβ assembly has attracted great attention recently. In this work, we use monocyanine fluorophore as the lead structure to develop a set of deep red carbazole-based cyanine molecules, which can specifically bind with Aβ fibril electrostatic and van der Waals interactions. Spectroscopic and microscopic characterizations demonstrate that one of these fluorophores, ()-1-(2-(2-methoxyethoxy)ethyl)-4-(2-(9-methyl-9H-carbazol-3-yl)vinyl) quinolinium iodide (me-slg) can bind to Aβ aggregates with strong fluorescence enhancement. The photophysical properties of me-slg at the single-molecule level, including low "on/off" duty cycle, high photon output, and sufficient switching cycles, enable real-time nanoscopic imaging of Aβ aggregates. Morphology-dependent toxic effect of Aβ aggregates toward PC12 cells is unveiled from nanoscopic fluorescence imaging. In addition, me-slg displays a strong inhibitory effect on Aβ fibrillation in a low inhibitor-protein ratio (.., I:P = 0.2). A noticeably reduced cytotoxic effect of Aβ after the addition of me-slg is also confirmed. These results afford promising applications in the design of a nanoscopic imaging probe for amyloid fibril as well as the development of inhibitors to modulate the fibrillation process.