Light-Wavelength-Based Quantitative Control of Dihydrofolate Reductase Activity by Using a Photochromic Isostere of an Inhibitor |
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Authors: | Takato Mashita Dr. Toshiyuki Kowada Hiroto Takahashi Prof. Dr. Toshitaka Matsui Prof. Dr. Shin Mizukami |
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Affiliation: | 1. Department of Chemistry, Graduate School of Science, Tohoku University, 6-3, Aoba, Aramaki, Aoba-ku, Sendai, Miyagi, 980–8578 Japan;2. Institute of Multidisciplinary Research for Advanced Materials, Tohoku University, 2-1-1, Katahira, Aoba-ku, Sendai, Miyagi, 980–8577 Japan |
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Abstract: | Photopharmacology has attracted research attention as a new tool for achieving optical control of biomolecules, following the methods of caged compounds and optogenetics. We have developed an efficient photopharmacological inhibitor—azoMTX—for Escherichia coli dihydrofolate reductase (eDHFR) by replacing some atoms of the original ligand, methotrexate, to achieve photoisomerization properties. This fine molecular design enabled quick structural conversion between the active “bent” Z isomer of azoMTX and the inactive “extended” E isomer, and this property afforded quantitative control over the enzyme activity, depending on the wavelength of irradiating light applied. Real-time photoreversible control over enzyme activity was also achieved. |
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Keywords: | azobenzenes enzyme catalysis inhibitors methotrexate photochromism photopharmacology |
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