Versatile near-infrared fluorescent probe for in vivo detection of Aβ oligomers

  • Bioorg Med Chem. 2020 Jul 1;28(13):115559. doi: 10.1016/j.bmc.2020.115559.
Fantian Zeng  1 ,  Jian Yang  1 ,  Xiaofang Li  1 ,  Kewen Peng  2 ,  Chongzhao Ran  3 ,  Yungen Xu  4 ,  Yuyan Li  5
Affiliations
  • 1. State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China; Jiangsu Key Laboratory of Drug Design and Optimization, Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing 21198, China.
  • 2. Jiangsu Key Laboratory of Drug Design and Optimization, Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing 21198, China.
  • 3. Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02129, USA.
  • 4. State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China; Jiangsu Key Laboratory of Drug Design and Optimization, Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing 21198, China. Electronic address: [email protected].
  • 5. State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China; Jiangsu Key Laboratory of Drug Design and Optimization, Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing 21198, China. Electronic address: [email protected].
PMID: 32546301 DOI: 10.1016/j.bmc.2020.115559
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 (Kd = 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.

Keywords
Alzheimer’s disease; Amyloid-β oligomers; Near-infrared fluorescent probe.
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