Department of Chemistry, Graduate School of Science, Tohoku University, 6-3, Aoba, Aramaki, Aoba-ku, Sendai, Miyagi, 980-8578, Japan.
Institute of Multidisciplinary Research for Advanced Materials, Tohoku University, 2-1-1, Katahira, Aoba-ku, Sendai, Miyagi, 980-8577, Japan.
Chembiochem. 2019 Jun 3;20(11):1382-1386. doi: 10.1002/cbic.201800816. Epub 2019 Apr 3.
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.
光药理学作为一种新的工具，用于实现对生物分子的光学控制，继笼状化合物和光遗传学方法之后，引起了研究关注。我们通过替换原始配体甲氨蝶呤的一些原子，开发了一种高效的光药理学抑制剂-偶氮 MTX-用于大肠杆菌二氢叶酸还原酶（eDHFR），以实现光致异构化性质。这种精细的分子设计使偶氮 MTX 的活性“弯曲”Z 异构体和非活性“伸展”E 异构体之间能够快速进行结构转换，并且根据应用的照射光的波长，可以对酶活性进行定量控制。还实现了对酶活性的实时光可逆控制。
