Institute for Research in Biomedicine (IRB Barcelona), Barcelona Institute of Science and Technology (BIST), Baldiri Reixac 10, 08028, Barcelona, Spain.
Laboratori de Química Orgànica, Facultat de Farmàcia, IBUB, Universitat de Barcelona, 08028, Barcelona, Spain.
Chemistry. 2021 Sep 9;27(51):12987-12991. doi: 10.1002/chem.202102370. Epub 2021 Jul 22.
The introduction of a novel tetra-ortho-chloroazobenzene amino acid (CEBA) has enabled photoswitching of the antimicrobial activity of tyrocidine A analogues by using exclusively visible light, granting spatiotemporal control under benign conditions. Compounds bearing this photoswitchable amino acid become active upon irradiation with red light, but quickly turn-off upon exposure to other visible light wavelengths. Critically, sunlight quickly triggers isomerisation of the red light-activated compounds into their original trans form, offering an ideal platform for self-deactivation upon release into the environment. Linear analogues of tyrocidine A were found to provide the best photocontrol of their antimicrobial activity, leading to compounds active against Acinetobacter baumannii upon isomerisation. Exploration of their N- and C-termini has provided insights into key elements of their structure and has allowed obtaining new antimicrobials displaying excellent strain selectivity and photocontrol.
引入了一种新型的四邻氯偶氮苯氨基酸（CEBA），通过仅使用可见光即可实现 tyrocidine A 类似物的抗菌活性的光开关切换，从而在良性条件下实现时空控制。含有这种光开关氨基酸的化合物在红光照射下具有活性，但在暴露于其他可见光波长下会迅速失活。关键的是，阳光会迅速促使红光激活化合物的顺反异构化为其原始的反式形式，为在释放到环境中后自动失活提供了理想的平台。发现 tyrocidine A 的线性类似物可以最好地控制其抗菌活性的光开关切换，从而导致在异构化后对鲍曼不动杆菌具有活性的化合物。对其 N-和 C-末端的探索提供了对其结构关键要素的深入了解，并允许获得显示出优异的菌株选择性和光控性的新型抗菌药物。
