Rational Design of a Long-Wavelength Fluorescent Probe for Highly Selective Sensing of Carboxylesterase 1 in Living Systems

2019 
Rational design of practical probes with excellent specificity and improved optical properties for a particular enzyme is always a big challenge. Herein, a practical and highly specific fluorescent probe for carboxylesterase 1 (CES1) was rationally designed using meso-carboxyl-BODIPY as the basic fluorophore based on the substrate preference and catalytic properties of CES1. Following molecular docking-based virtual screening combined with reaction phenotyping-based experimental screening, we found that MMB (probe 7) exhibited the optimal combination of sensitivity and specificity towards human CES1 in contrast to other ester derivatives. Under physiological conditions, MMB could be readily hydrolyzed by CES1 and released MCB, such biotransformation brought great changes in electronic properties at meso-position of the fluorophore and triggered a dramatic increase in fluorescence emission around 595 nm. Moreover, MMB was cell membrane permeable and was successfully applied to monitor the real activities o...
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