A BODIPY-based probe for amyloid-β imaging in vivo

Mingguang Zhu; Guoyang Zhang; Ziwei Hu; Chaofeng Zhu; Yixiang Chen; Tony D. James; Lijun Ma; Zhuo Wang

doi:10.1039/d2qo02032g

A BODIPY-based probe for amyloid-β imaging in vivo

Mingguang Zhu, Guoyang Zhang, Ziwei Hu, Chaofeng Zhu, Yixiang Chen, Tony D. James, Lijun Ma, Zhuo Wang

Department of Chemistry

Research output: Contribution to journal › Article › peer-review

Abstract

Alzheimer's disease (AD) is a neurodegenerative disease, and the efficient detection of amyloid-β (Aβ) plaques can greatly enhance diagnosis and therapy. Most reported probes used to detect Aβ are based on the N,N-dimethylamino group. As such, the design of new Aβ-recognition units facilitates the recognition of Aβ. Herein, we present an Aβ recognition unit [4-(Boc-amino) benzene] used to develop BocBDP. BocBDP can recognize and image Aβ plaques both in vitro and in vivo through the interaction with amino acid residues Lys16 (K16), Val18 (V18), and Glu22 (E22). The hydrogen bonding interaction (1.9 Å) between the carbonyl oxygen atom in the Boc unit and the amino acid residue K16 allows BocBDP to bind strongly to Aβ, resulting in a five-fold fluorescence enhancement and a high affinity (K_d = 67.8 ± 3.18 nM). BocBDP can cross the BBB and image Aβ for at least 2 hours. We anticipate that our Aβ recognition unit will help improve the design of probes that specifically recognize Aβ.

Original language	English
Pages (from-to)	1903-1909
Journal	Organic Chemistry Frontiers
Volume	10
Early online date	10 Mar 2023
DOIs	https://doi.org/10.1039/d2qo02032g
Publication status	Published - 21 Apr 2023

ASJC Scopus subject areas

Organic Chemistry

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title = "A BODIPY-based probe for amyloid-β imaging in vivo",

abstract = "Alzheimer's disease (AD) is a neurodegenerative disease, and the efficient detection of amyloid-β (Aβ) plaques can greatly enhance diagnosis and therapy. Most reported probes used to detect Aβ are based on the N,N-dimethylamino group. As such, the design of new Aβ-recognition units facilitates the recognition of Aβ. Herein, we present an Aβ recognition unit [4-(Boc-amino) benzene] used to develop BocBDP. BocBDP can recognize and image Aβ plaques both in vitro and in vivo through the interaction with amino acid residues Lys16 (K16), Val18 (V18), and Glu22 (E22). The hydrogen bonding interaction (1.9 {\AA}) between the carbonyl oxygen atom in the Boc unit and the amino acid residue K16 allows BocBDP to bind strongly to Aβ, resulting in a five-fold fluorescence enhancement and a high affinity (Kd = 67.8 ± 3.18 nM). BocBDP can cross the BBB and image Aβ for at least 2 hours. We anticipate that our Aβ recognition unit will help improve the design of probes that specifically recognize Aβ.",

author = "Mingguang Zhu and Guoyang Zhang and Ziwei Hu and Chaofeng Zhu and Yixiang Chen and James, {Tony D.} and Lijun Ma and Zhuo Wang",

note = "Funding Information: We are thankful for the support from the Beijing Natural Science Foundation (No. 7232342), the Natural Science Foundation of China (No. 82131430174 and 81961138011), the Academy of Medical Sciences Newton Advanced Fellowship (NAFR13\1015), the National Key Research and Development Program of China (2021YFC2101500), and the China Scholarship Council. TDJ wishes to thank the Royal Society for a Wolfson Research Merit Award and the Open Research Fund of the School of Chemistry and Chemical Engineering, Henan Normal University for support (2020ZD01). ",

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doi = "10.1039/d2qo02032g",

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AU - Zhu, Mingguang

AU - Zhang, Guoyang

AU - Hu, Ziwei

AU - Zhu, Chaofeng

AU - Chen, Yixiang

AU - James, Tony D.

AU - Ma, Lijun

AU - Wang, Zhuo

N1 - Funding Information: We are thankful for the support from the Beijing Natural Science Foundation (No. 7232342), the Natural Science Foundation of China (No. 82131430174 and 81961138011), the Academy of Medical Sciences Newton Advanced Fellowship (NAFR13\1015), the National Key Research and Development Program of China (2021YFC2101500), and the China Scholarship Council. TDJ wishes to thank the Royal Society for a Wolfson Research Merit Award and the Open Research Fund of the School of Chemistry and Chemical Engineering, Henan Normal University for support (2020ZD01).

PY - 2023/4/21

Y1 - 2023/4/21

N2 - Alzheimer's disease (AD) is a neurodegenerative disease, and the efficient detection of amyloid-β (Aβ) plaques can greatly enhance diagnosis and therapy. Most reported probes used to detect Aβ are based on the N,N-dimethylamino group. As such, the design of new Aβ-recognition units facilitates the recognition of Aβ. Herein, we present an Aβ recognition unit [4-(Boc-amino) benzene] used to develop BocBDP. BocBDP can recognize and image Aβ plaques both in vitro and in vivo through the interaction with amino acid residues Lys16 (K16), Val18 (V18), and Glu22 (E22). The hydrogen bonding interaction (1.9 Å) between the carbonyl oxygen atom in the Boc unit and the amino acid residue K16 allows BocBDP to bind strongly to Aβ, resulting in a five-fold fluorescence enhancement and a high affinity (Kd = 67.8 ± 3.18 nM). BocBDP can cross the BBB and image Aβ for at least 2 hours. We anticipate that our Aβ recognition unit will help improve the design of probes that specifically recognize Aβ.

AB - Alzheimer's disease (AD) is a neurodegenerative disease, and the efficient detection of amyloid-β (Aβ) plaques can greatly enhance diagnosis and therapy. Most reported probes used to detect Aβ are based on the N,N-dimethylamino group. As such, the design of new Aβ-recognition units facilitates the recognition of Aβ. Herein, we present an Aβ recognition unit [4-(Boc-amino) benzene] used to develop BocBDP. BocBDP can recognize and image Aβ plaques both in vitro and in vivo through the interaction with amino acid residues Lys16 (K16), Val18 (V18), and Glu22 (E22). The hydrogen bonding interaction (1.9 Å) between the carbonyl oxygen atom in the Boc unit and the amino acid residue K16 allows BocBDP to bind strongly to Aβ, resulting in a five-fold fluorescence enhancement and a high affinity (Kd = 67.8 ± 3.18 nM). BocBDP can cross the BBB and image Aβ for at least 2 hours. We anticipate that our Aβ recognition unit will help improve the design of probes that specifically recognize Aβ.

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A BODIPY-based probe for amyloid-β imaging in vivo

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