Picomolar-sensitive β-amyloid fibril fluorophores by tailoring the hydrophobicity of biannulated π-elongated dioxaborine-dyes

Jusung An, Peter Verwilst, Hira Aziz, Jinwoo Shin, Sungsu Lim, Ilwha Kim, Yun Kyung Kim, Jong Seung Kim

Research output: Contribution to journalArticlepeer-review

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 Aβ1-42 fibrils —while concurrently preventing poor aqueous solubility—via biannulate donor motifs in D-π-A dyes. An unprecedented sub-nanomolar affinity was found (Kd = 0.62 ± 0.33 nM) and applied to super-sensitive and red-emissive fluorescent staining of amyloid plaques in cortical brain tissue ex vivo. These fluorophores expand the dioxaborine-curcumin-based family of Aβ-sensitive fluorophores with a promising new imaging agent.

Original languageEnglish
JournalBioactive Materials
DOIs
Publication statusAccepted/In press - 2021

Keywords

  • Alzheimer's disease
  • Dioxaborine-dye
  • Hydrophobicity tailoring
  • Small-molecular fluorescent probe
  • β-Amyloid

ASJC Scopus subject areas

  • Biotechnology
  • Biomaterials
  • Biomedical Engineering

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