Funct. Mater. 2022; 29 (2): 252-262.
Synthetic and natural flavonols as promising fluorescence probes for β-glucosidase activity screening
1Institute of Chemistry and School of Chemistry, V.N.Karazin Kharkiv National University, 4 Svobody Sq., 61022 Kharkiv, Ukraine
2State Scientific Institution Institute for Single Crystals, National Academy of Sciences of Ukraine, 60 Nauky Ave., 61072 Kharkiv, Ukraine
Natural and synthetic flavonols are environmentally sensitive dyes whose emission properties are highly sensitive to their immediate environment. Here we describe the synthesis and spectral properties of flavonols bearing a series of substituents in the 4`-aryl ring. The synthesized flavonols were applied to study their capability for fluorescence sensing of β-glucosidase in physiological solutions. We found that 4`-fluoro- and 4`-carboxyflavonols revealed the essential fluorescence enhancement in the presence of β-glucosidase, which is characteristic of the protein-induced turn-on effect. The fluorescence titration experiments suggest that the studied flavonols favor binding to the protein, so that the probes leave a polar aqueous solution and enters a nonpolar hydrophobic environment inside a protein pocket. These findings were collaborated by molecular docking calculations, which allowed us to identify favorable binding modes and the binding affinity of the synthetic flavonols towards β-glucosidases from various sources. Molecular docking revealed the high binding affinity towards β-glucosidase, which is the same order of magnitude as the well-known natural flavonols. Our results suggest that the studied flavonol dyes can be a promising scaffold for developing novel flavonol glycosides as turn on/off fluorescent indicators of β-glucosidase activity.
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