A molecular approach to rationally constructing specific fluorogenic substrates for the detection of acetylcholinesterase activity in live cells, mice brains and tissues

Xiaofeng Wu, Jong Min An, Jizhen Shang, Eugene Huh, Sujie Qi, Eunhye Lee, Haidong Li, Gyoungmi Kim, Huimin Ma, Myung Sook Oh, Dokyoung Kim, Juyoung Yoon

Research output: Contribution to journalArticlepeer-review

39 Scopus citations

Abstract

Acetylcholinesterase (AChE) is an extremely critical hydrolase tightly associated with neurological diseases. Currently, developing specific substrates for imaging AChE activity still remains a great challenge due to the interference from butyrylcholinesterase (BChE) and carboxylesterase (CE). Herein, we propose an approach to designing specific substrates for AChE detection by combining dimethylcarbamate choline with a self-immolative scaffold. The representative P10 can effectively eliminate the interference from CE and BChE. The high specificity of P10 has been proved via imaging AChE activity in cells. Moreover, P10 can also be used to successfully map AChE activity in different regions of a normal mouse brain, which may provide important data for AChE evaluation in clinical studies. Such a rational and effective approach can also provide a solid basis for designing probes with different properties to study AChE in biosystems and another way to design specific substrates for other enzymes.

Original languageEnglish
Pages (from-to)11285-11292
Number of pages8
JournalChemical Science
Volume11
Issue number41
DOIs
StatePublished - 7 Nov 2020

Bibliographical note

Funding Information:
All of the experiments performed with mice were carried out in accordance with the National Institute of Health Guide for the Care and Use of Laboratory Animals (NIH Publications No. 80-23) revised in 1996 and protocols approved by the Institutional Animal Care and Use Committee of Kyung Hee University [KHUASP(SE)-19-002]. J. Y. thanks the National Research Foundation of Korea (NRF), which was funded by the Korea government (MSIP) (No. 2012R1A3A2048814). D. K. acknowledges the financial support from the NRF of Korea (No. 2019-M3A9H1103783, No. 2018-M3A9H3021707, and No. 2018-R1A6A1A03025124). O. M. S. acknowledges the support from the Medical Research Center Program through the NRF of Korea funded by the Ministry of Science and ICT (No. 2017-R1A5A2014768). H. M. M. thanks the National Natural Science Foundation of China (No. 21820102007).

Funding Information:
All of the experiments performed with mice were carried out in accordance with the National Institute of Health Guide for the Care and Use of Laboratory Animals (NIH Publications No. 80-23) revised in 1996 and protocols approved by the Institutional Animal Care and Use Committee of Kyung Hee University [KHUASP(SE)-19-002]. J. Y. thanks the National Research Foundation of Korea (NRF), which was funded by the Korea government (MSIP) (No. 2012R1A3A2048814). D. K. acknowledges the nancial support from the NRF of Korea (No. 2019-M3A9H1103783, No. 2018-M3A9H3021707, and No. 2018-R1A6A1A03025124). O. M. S. acknowledges the support from the Medical Research Center Program through the NRF of Korea funded by the Ministry of Science and ICT (No. 2017-R1A5A2014768). H. M. M. thanks the National Natural Science Foundation of China (No. 21820102007).

Publisher Copyright:
© The Royal Society of Chemistry.

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