Picomolar-sensitive β-amyloid fibril fluorophores by tailoring the hydrophobicity of biannulated π-elongated dioxaborine-dyes.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 35224305.
- Also identified by DOI 10.1016/j.bioactmat.2021.10.047 and PMC identifier 8845109.
- Licence recorded as CC BY-NC-ND.
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Abstract
The pathological origin of Alzheimer's disease (AD) is still shrouded in mystery, despite intensive worldwide research efforts. The selective visualization of β-amyloid (Aβ), the most abundant proteinaceous deposit in AD, is pivotal to reveal AD pathology. To date, several small-molecule fluorophores for Aβ species have been developed, with increasing binding affinities. In the current work, two organic small-molecule dioxaborine-derived fluorophores were rationally designed through tailoring the hydrophobicity with the aim to enhance the binding affinity for Aβ<sub>1-42</sub> fibrils -while concurrently preventing poor aqueous solubility-<i>via</i> biannulate donor motifs in D-π-A dyes. An unprecedented sub-nanomolar affinity was found (<i>K</i> <sub>d</sub> = 0.62 ± 0.33 nM) and applied to super-sensitive and red-emissive fluorescent staining of amyloid plaques in cortical brain tissue <i>ex vivo</i>. These fluorophores expand the dioxaborine-curcumin-based family of Aβ-sensitive fluorophores with a promising new imaging agent.