A Comparative Photophysical Study of Structural Modifications of Thioflavin T-Inspired Fluorophores.,The Journal of Physical Chemistry Letters

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A Comparative Photophysical Study of Structural Modifications of Thioflavin T-Inspired Fluorophores.
The Journal of Physical Chemistry Letters ( IF 4.8 ) Pub Date : 2020-09-14 , DOI: 10.1021/acs.jpclett.0c01549
Lisa-Maria Needham ₁ , Judith Weber _{1,

2,

3} , Colin M Pearson ₄ , Dung T Do ₄ , Felix Gorka ₁ , Guanpeng Lyu ₁ , Sarah E Bohndiek ₂ , Thomas N Snaddon ₄ , Steven F Lee ₁

Affiliation

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.

中文翻译：

硫黄素 T 激发的荧光团结构修饰的比较光物理研究。

苯并噻唑盐、硫磺素 T (ThT) 已被广泛采用作为体外淀粉样蛋白的“金标准”荧光报告剂。它作为分子转子的特性导致在与淀粉样蛋白中的 β-折叠结合后产生大规模（约 1000 倍）的荧光开启。然而，ThT 的复杂光物理学与淀粉样蛋白结合基序的复杂性和多样性相结合，意味着人们对这些相互作用知之甚少。为了研究这一类重要的荧光团，我们对淀粉样蛋白 (PAP) 的 12 种受 ThT 启发的荧光探针的新型库进行了详细的光物理表征和比较，其中杂环和氨基苯成分的电荷和供体能力均已被询问，分别。这使得两个结构基团能够直接光物理并置：中性“PAP”（1 类）和带电“mPAP”荧光团（2 类）。我们在整体和单聚集体水平上量化了结合和光学特性，一些衍生物表现出比 ThT 更高的聚集体亲和力和亮度。最后，我们展示了他们以 ~16 nm 的定位精度对 α-突触核蛋白原纤维进行超分辨率成像的能力。这些衍生物的性质为苯并噻唑探针的化学结构和功能之间的关系提供了新的见解。

更新日期：2020-10-02

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