Rational design of α-glucosidase activated near-infrared fluorescent probe and its applications in diagnosis and treatment of diabetes

alpha-Glucosidase (alpha-GLC) as a key hydrolase plays an important role in controlling blood glucose. In this work, we developed a alpha-GLC-activated near-infrared fluorescent probe HCBG by rational design and chemical molecular docking. HCBG showed excellent selectivity and sensitivity toward alpha-GLC in complex bio-samples. With the advantage of its good cell permeability realizing the in situ real-time imaging of alpha-GLC in intestinal microorganism, living cells, and animals. Importantly, 5 human fungi with high alpha-GLC expression were successfully screened out and imaged from 57 human intestinal fungi. More importantly, among them, the intestine colonization of M2204 and PB005A in animal can significantly influence glucose metabolism in intestine further increase the blood glucose levels to 9.1 mmol/L. Finally, using the high-throughput screening system established by HCBG, 1-Deoxynojirimycin as a natural inhibitor of alpha-GLC was isolated and identified, and IC50 is 1.58 mu M. In summary, this study provides a novel fluorescence visualization tool for discovering and exploring the biological functions of diabetes-related gut microbiota and the high-throughput screening approach for alpha-GLC inhibitor.

Automated summary

In this study, a near-infrared fluorescent probe HCBG was developed for imaging of alpha-GLC. HCBG exhibited excellent selectivity and sensitivity towards alpha-GLC in complex bio-samples, and showed good cell permeability for in situ real-time imaging. Through the high-throughput screening system established by HCBG, a natural alpha-GLC inhibitor was successfully isolated and identified. This study provides a novel fluorescence visualization tool for discovering and exploring the biological functions of diabetes-related gut microbiota, and a high-throughput screening approach for alpha-GLC inhibitor.