A Comparative Photophysical Study of Structural Modifications of Thioflavin T-Inspired Fluorophores

The benzothiazolium salt, Thioflavin T (ThT), has been widely adopted as the "gold-standard" fluorescent reporter of amyloid in vitro. Its properties as a molecular rotor result in a large-scale (∼1000-fold) fluorescence turn-on upon binding to β-sheets in amyloidogenic proteins. However, the complex photophysics of ThT combined with the intricate and varied nature of the amyloid binding motif means these interactions are poorly understood. To study this important class of fluorophores, we present a detailed photophysical characterization and comparison of a novel library of 12 ThT-inspired fluorescent probes for amyloid protein (PAPs), where both the charge and donor capacity of the heterocyclic and aminobenzene components have been interrogated, respectively. This enables direct photophysical juxtaposition of two structural groups: the neutral "PAP" (class 1) and the charged "mPAP" fluorophores (class 2). We quantify binding and optical properties at both the bulk and single-aggregate levels with some derivatives showing higher aggregate affinity and brightness than ThT. Finally, we demonstrate their abilities to perform super-resolution imaging of α-synuclein fibrils with localization precisions of ∼16 nm. The properties of the derivatives provide new insights into the relationship between chemical structure and function of benzothiazole probes.

Medienart:

E-Artikel

Erscheinungsjahr:

2020

Erschienen:

2020

Enthalten in:

Zur Gesamtaufnahme - volume:11

Enthalten in:

The journal of physical chemistry letters - 11(2020), 19 vom: 01. Okt., Seite 8406-8416

Sprache:

Englisch

Beteiligte Personen:

Needham, Lisa-Maria [VerfasserIn]
Weber, Judith [VerfasserIn]
Pearson, Colin M [VerfasserIn]
Do, Dung T [VerfasserIn]
Gorka, Felix [VerfasserIn]
Lyu, Guanpeng [VerfasserIn]
Bohndiek, Sarah E [VerfasserIn]
Snaddon, Thomas N [VerfasserIn]
Lee, Steven F [VerfasserIn]

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Volltext

Themen:

Journal Article

Anmerkungen:

Date Completed 05.10.2020

Date Revised 10.02.2024

published: Print-Electronic

Citation Status PubMed-not-MEDLINE

doi:

10.1021/acs.jpclett.0c01549

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM314965645