Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University, 46-29 Yoshida Shimoadachi-cho, Sakyo-ku, Kyoto 606-8501, Japan.
J Med Chem. 2023 Oct 26;66(20):14029-14046. doi: 10.1021/acs.jmedchem.3c01057. Epub 2023 Oct 12.
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 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 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 NIRF imaging of diverse soluble Aβ aggregates.
可溶性淀粉样β（Aβ）聚集物，被认为是 Aβ 最具毒性的形式，引起了人们对其作为阿尔茨海默病（AD）治疗靶点和生物标志物的关注。由于可溶性 Aβ 聚集物是短暂且多样化的，因此对其多样化形式进行成像有望对 AD 的研究和诊断产生显著影响。在这里，我们报告了一种针对多种可溶性 Aβ 聚集物的近红外荧光（NIRF）探针 BAOP-16。BAOP-16 的分子形状类似于“y”，在近红外区域与可溶性 Aβ 聚集物结合时，其荧光强度显著选择性增加，并且对其具有高结合亲和力。此外，BAOP-16 可以检测到接种 Aβ 的模型小鼠大脑中的 Aβ 低聚物。在 BAOP-16 的荧光成像研究中，AD 模型小鼠的大脑显示出比野生型小鼠更高的荧光信号。这些结果表明，BAOP-16 可用于多种可溶性 Aβ 聚集物的 NIRF 成像。
