Tailoring Hydrophobicity of Thioflavin T to Optimize Aβ Fibril Bioimaging

Fluorescence imaging of amyloid beta (Aβ) polypeptide using a small‐molecule fluorophore is a practical system for Alzheimer's disease (AD) diagnosis in clinical and research fields. Herein, a molecular designing strategy for a new fluorogenic probe that equips bathochromic emission shift and e...

Full description

Saved in:
Bibliographic Details
Published in:Advanced NanoBiomed Research (Online) 2023-06, Vol.3 (6), p.n/a
Main Authors: Zunbul, Zehra, An, Jusung, Aziz, Hira, Shin, Jinwoo, Lim, Sungsu, Yu, Le, Kim, Yun Kyung, Kim, Jong Seung
Format: Article
Language:English
Subjects:
Affinity
Alzheimer's disease
Amino acids
amyloid beta
Binding
Binding sites
Charge transfer
Dementia
Emission
Fibrils
Fluorescence
Fluorescent dyes
Fluorescent indicators
Hydrophobicity
hydrophobicity tailoring
Ligands
Medical imaging
Neurodegenerative diseases
Polypeptides
Signal to noise ratio
small-molecule fluorescent probes
Software
Transgenic animals
twisted intramolecular charge transfer
β-Amyloid
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Fluorescence imaging of amyloid beta (Aβ) polypeptide using a small‐molecule fluorophore is a practical system for Alzheimer's disease (AD) diagnosis in clinical and research fields. Herein, a molecular designing strategy for a new fluorogenic probe that equips bathochromic emission shift and enhanced binding affinity toward Aβ fibril through structural optimization is suggested. Thioflavin T (ThT)‐derived fluorescent dyes are developed by adjusting the hydrophobicity of electron donor moiety in D–π–A structures with biannulated ring expansion. Indeed, probes are tuned to have redshifted fluorescence emission wavelength and optimized binding affinities for Aβ fibrils in vitro and cortical imaging. Detection of background signal is minimized by maintaining the photophysical properties of twisted intramolecular charge transfer (TICT), resulting in significantly sensitive fluorogenic probes for outstanding bioimaging in AD. The synthesis and development of thioflavin T derivatives are suggested for tailoring hydrophobicity by substituting biannulated electron donor moieties, which enables the formation of a D–π–A molecular structure. In particular, a novel fluorophore, ThN, can detect amyloid beta fibrils as bathochromic emission and clear visualization of stained amyloid beta aggregates co‐occurrence with tau proteins in brain slice images.
ISSN:2699-9307
2699-9307
DOI:10.1002/anbr.202200161