Versatile near-infrared fluorescent probe for in vivo detection of Aβ oligomers. Issue 13 (1st July 2020)

• Record Type: Journal Article
• Authors: Zeng, Fantian; Yang, Jian; Li, Xiaofang; Peng, Kewen; Ran, Chongzhao; Xu, Yungen; Li, Yuyan
• Is Part Of: Bioorganic & medicinal chemistry. Volume 28:Issue 13(2020)
• Publication Date: 2020-07-01
• Subjects: Amyloid-β oligomers -- Alzheimer's disease -- Near-infrared fluorescent probe; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; Chemistry, Clinical -- Periodicals; Chemistry, Organic -- Periodicals; Chimie bio-organique -- Périodiques; Chimie pharmaceutique -- Périodiques; 615.19
• DOI: 10.1016/j.bmc.2020.115559
• Languages: English
• ISSNs: 0968-0896

Abstract

Graphical abstract: We developed a versatile NIR fluorescence probe PTO-41 for the detection of Aβ oligomers with high selectivity and excellent fluorescent properties. This probe could differentiate between 4 month-old APP/PS1 transgenic mice from wild-type mice during in vivo imaging. Highlights: The probe PTO-41 is a versatile NIR fluorescent probe for the detection of Aβ oligomers. The probe PTO-41 exhibits excellent functional properties both in vitro and in vivo. This probe PTO-41 has been successfully applied for the in vivo NIR fluorescent imaging of Aβ oligomers in 4 month-old APP/PS1 and differentiating from WT mice. Abstract: Amyloid-β oligomers (AβOs) enrichment in brain is highly related to Alzheimer's pathogenesis, but tracing them in the brain by imaging technique is still a great challenge due to their heterogeneity and metastability. Herein, a new near-infrared (NIR) fluorescent probe, namely, PTO-41, was designed and synthesized to specifically target AβOs. PTO-41 possesses excellent functional properties including optimal fluorescent properties (emission maxima at 680 nm upon interacting with AβOs), high affinity ( K d = 349 nM), low cell toxicity, desirable lipophilicity (log P = 2.24), and fast wash out from the brain (brain2 min /brain60 min = 5.0). Furthermore, PTO-41 exhibits a high sensitivity toward AβOs in vitro phantom imaging experiments. More importantly, PTO-41 shows great capacity to differentiate between 4-month-old APP/PS1 model mice from age-matched control mice using in vivo imaging. In summary, PTO-41 almost meets all the requirements as a versatile NIR fluorescent probe for the detection of AβOs both in vitro and in vivo .