| Abstrakt: |
Amyloid protein aggregation is associated with many neurodegenerative diseases, including amyloid‐β (Aβ) in Alzheimer disease, human islet amyloid polypeptide (hIAPP) in type II diabetes, and human calcitonin (hCT) in medullary thyroid carcinoma. Significant efforts have been made to develop different diagnostic and prevention strategies for the early detection and intervention of these disease‐causative protein aggregates. However, conventional design wisdoms are mostly limited to the molecules with either single function (amyloid imaging or amyloid prevention) or single targeting protein (Aβ, hIAPP, or hCT). Here, a rational design strategy of an amyloid‐aggregation‐induced emission (AIE)‐active molecule is demonstrated by conjugating an amyloid fragment of GNNQQNY (G7) with an AIE fluorescent molecule of triphenylvinyl benzoic acid (namely, G7‐TBA), making G7‐TBA as multiple‐target, dual‐function, amyloid probes and amyloid modulators for detecting, monitoring, and altering amyloid aggregation of three different amyloid proteins (Aβ, hIAPP, and hCT). G7‐TBA probe shows conformationally specific binding affinities to amyloid aggregates, switching from an "off" state (low fluorescence) for amyloid monomers to an "on" state (high fluorescence) for β‐structure‐rich amyloid oligomers and fibrils in aqueous solution. Further surface immobilization of TBA probes on surface plasmon resonance surfaces allows to amplify detection sensitivity and binding affinity to amyloid aggregates formed at different aggregation stages. G7‐TBA as amyloid modulator enables acceleration of amyloid fibrillization and selectively protects cells from hIAPP‐induced toxicity. The distinct amyloid detection and modulation of G7‐TBA are essentially derived from the cross‐seeding between G7 and amyloid aggregation via β‐structure interaction, which by far exceed the binding affinity between commercial ThT and amyloid aggregates. Such design concepts of amyloid‐AIE conjugates can be further explored as multiple‐function and target probes and/or modulators for biomedical applications. [ABSTRACT FROM AUTHOR] |
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