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Different structure-oriented design of selective butyrylcholinesterase probe and its application in drug discovery

Joint Event on 15th World Congress on Biotechnology And Biotech Industries Meet and 2nd International Conference on Enzymology and Molecular Biology

Wen-Chao Yang, Shu-Hou Yang, Qi Sun and Guang-Fu Yang

Central China Normal University, China

Posters & Accepted Abstracts: J Biotechnol Biomater

DOI: 10.4172/2155-952X.C1.071

Abstract
The two major human cholinesterases are acetylcholinesterase (AChE; EC 3.1.1.7) and butyrylcholinesterase (BChE; EC 3.1.1.8), and are very important enzymes in multiple areas such as pharmacology, neurobiology and toxicology due to their significant roles in human body and health. Although the biological function is uncertain, the BChE levels have been implicated in lipid metabolism and various human diseases such as liver damage, cirrhosis, Alzheimer��?s disease (AD) and liver metastasis. BChE is also responsible for detoxifying xenobiotics like organophosphates and cocaine and is a well-known biomarker for clinical diagnosis. Thus, the quantification of BChE activity and its inhibition is not only important in diseases diagnosis, but also indispensable for drug discovery. We report on the different structure-oriented design and application of a selective fluorogenic molecular probe (BChEFP) for human butyrylcholinesterase (BChE). This probe, rationally designed by mimicking the native substrate and manipulating the steric feature of the recognition group of designed probes targeting the structural difference of the active sites for BChE and acetylcholinesterase (AChE), exhibits near-zero background fluorescence but produce remarkable fluorescence enhancement upon the catalysis by BChE in a fast biochemical reaction. To the best of our knowledge, BChE-FP is the first probe that can discriminate BChE from AChE, which is successfully applied for BChE inhibitor screening and characterization under physiological conditions, and BChE detection in human serum. These results demonstrate that this molecular probe can function as a useful molecular tool for high-throughput drug discovery against BChE-related diseases, as well as the biosensing for neuromuscular blocking agents.
Biography

Email: tomyang@mail.ccnu.edu.cn

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