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

Fantian Zeng; Jian Yang; Xiaofang Li; Kewen Peng; Chongzhao Ran; Yungen Xu; Yuyan Li

doi:10.1016/j.bmc.2020.115559

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. Epub 2020 May 12.

Authors

Fantian Zeng¹, Jian Yang¹, Xiaofang Li¹, Kewen Peng², Chongzhao Ran³, Yungen Xu⁴, Yuyan Li⁵

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: xu_yungen@hotmail.com.
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: yuyanli@cpu.edu.cn.

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 (K_d = 349 nM), low cell toxicity, desirable lipophilicity (log P = 2.24), and fast wash out from the brain (brain_{2 min}/brain_{60 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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Alzheimer Disease / diagnostic imaging*
Amyloid beta-Peptides / analysis*
Animals
Blood-Brain Barrier / metabolism
Borinic Acids / chemical synthesis*
Borinic Acids / metabolism
Brain / metabolism
Cell Survival
Disease Models, Animal
Female
Fluorescent Dyes / chemical synthesis*
Fluorescent Dyes / metabolism*
Humans
In Vitro Techniques
Infrared Rays
Mice
Mice, Inbred C57BL
Molecular Structure
Optical Imaging

Substances

Amyloid beta-Peptides
Borinic Acids
Fluorescent Dyes