Soluble amyloid β (Aβ) aggregates have attracted attention as therapeutic targets and biomarkers of Alzheimer's disease. We previously reported a fluorescent probe, BAOP-16, which targets soluble Aβ aggregates. However, its limited aqueous solubility has hindered its application in biological assays. In this study, we developed aqueous-soluble fluorescent probes that target soluble Aβ aggregates. Among the synthesized candidates, sBAOP-2-3, which is substituted with two CH₂C^-Tf₂ groups and a diphenyl amino group, exhibited markedly improved aqueous solubility compared with BAOP-16. It also showed a marked increase in fluorescence intensity in the presence of Aβ oligomers, and the highest selectivity for Aβ oligomers over Aβ fibrils. During the aggregation process of Aβ, sBAOP-2-3 detected soluble Aβ aggregates in an early phase. Furthermore, staining experiments using mouse brain sections suggested that sBAOP-2-3 selectively stained soluble Aβ aggregates in mouse brains. These results suggest that sBAOP-2-3 shows promise as a probe for the selective detection of soluble Aβ aggregates in biological systems.

2023-10-26·Journal of medicinal chemistry1区 · 医学

In Vivo Near-Infrared Fluorescence Imaging Selective for Soluble Amyloid β Aggregates Using y-Shaped BODIPY Derivative.

1区 · 医学

Article

作者: Ono, Masahiro ; Watanabe, Hiroyuki ; Akasaka, Takahiro

Soluble amyloid β (Aβ) aggregates, suggested to be the most toxic forms of Aβ, draw attention as therapeutic targets and biomarkers of Alzheimer's disease (AD). As soluble Aβ aggregates are transient and diverse, imaging their diverse forms in vivo is expected to have a marked impact on research and diagnosis of AD. Herein, we report a near-infrared fluorescent (NIRF) probe, BAOP-16, targeting diverse soluble Aβ aggregates. BAOP-16, whose molecular shape resembles "y", showed a marked selective increase in fluorescence intensity upon binding to soluble Aβ aggregates in the near-infrared region and a high binding affinity for them. Additionally, BAOP-16 could detect Aβ oligomers in the brains of Aβ-inoculated model mice. In an in vivo fluorescence imaging study of BAOP-16, brains of AD model mice displayed significantly higher fluorescence signals than those of wild-type mice. These results indicate that BAOP-16 could be useful for the in vivo NIRF imaging of diverse soluble Aβ aggregates.

100 项与 BAOP-16 相关的药物交易

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