Photoregulation of biomolecules has become crucial tools in chemical biology, because light enables access under mild conditions and with delicate spatiotemporal control. The control of enzyme activity in a reversible way is a challenge. To achieve it, a facile approach is to use photoswitchable inhibitors. This review highlights recent progress in photoswitchable inhibitors based on azobenzenes units. The progress suggests that the incorporation of an azobenzene unit to a known inhibitor is an effective method for preparing a photoswitchable inhibitor, and with these photoswitchable inhibitors, the activity of enzymes can be regulated by optical control, which is valuable in both basic science and therapeutic applications.
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http://dx.doi.org/10.3390/molecules29194523 | DOI Listing |
Coord Chem Rev
January 2024
Department of Chemistry, University of Texas at Austin, 105 E 24th St, Austin, TX 78712, United States.
Metalloenzymes are responsible for numerous physiological and pathological processes in living organisms; however, there are very few FDA-approved metalloenzyme-targeting therapeutics (only ~ 67 FDA-approved metalloenzyme inhibitors as of 2020, less than ~ 5 % of all FDA-approved therapeutics). Most metalloenzyme inhibitors have been developed to target the catalytic metal centers in metalloenzymes the incorporation of metal-binding groups. Light-controlled inhibition of metalloenzymes has been used as a means to specifically activate and inactivate inhibitor engagement at a desired location and time light irradiation, allowing for precise spatiotemporal control over metalloenzyme activity.
View Article and Find Full Text PDFJ Phys Chem B
January 2025
Institute of Theoretical Chemistry, Faculty of Chemistry, University of Vienna, Währinger Str. 17, 1090 Vienna, Austria.
The photoisomerization dynamics of azo-escitalopram, a synthetic photoswitchable inhibitor of the human serotonin transporter, is investigated in both gas-phase and water. We use the trajectory surface hopping method─as implemented in SHARC─interfaced with the floating occupation molecular orbital-configuration interaction semiempirical method to calculate on-the-fly energies, forces, and couplings. The inclusion of explicit water molecules is enabled using an electrostatic quantum mechanics/molecular mechanics framework.
View Article and Find Full Text PDFInt J Mol Sci
November 2024
Institute of Organic and Medicinal Chemistry, Faculty of Pharmacy, University of Pécs, Honvéd útja 1, H-7624 Pécs, Hungary.
The therapeutical applicability of the anticancer drug phototrexate, a photoswitchable derivative of the antimetabolite dihydrofolate reductase inhibitor methotrexate, highly depends on the stability of its bioactive isomer. Considering that only the configuration of phototrexate is bioactive, in this work, the effect of the molecular environment on the stability of the isomer of this drug has been investigated. UV-vis absorption and fluorescence-based solvent relaxation methods have been used.
View Article and Find Full Text PDFMethods Mol Biol
December 2024
Graduate School of Life Science, Hokkaido University, Sapporo, Japan.
Photoswitchable compounds are potent tools for elucidating molecular functions in dynamic cellular processes. Photoswitchable inhibitors targeting various mitotic spindle factors have been developed. In this chapter, we describe experimental methods for photo-controlling mitotic chromosome dynamics using a recently developed photoswitchable inhibitor of mitotic kinesin, CENP-E.
View Article and Find Full Text PDFJ Agric Food Chem
December 2024
Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China.
Photopharmacology, an emerging interdisciplinary field, enables precise modulation of target biological activity by employing light-controllable photoswitchable molecules. The research on nicotinamidase (Naam), a recently identified target molecule for pesticides, remains relatively underexplored. Therefore, based on the structure of its inhibitor Flonicamid, we designed and synthesized a series of photopharmacological ligands (FAB) by incorporating a light-controllable azobenzene switch, further investigating their effects on insect behavior and activity.
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