Zhao Jie, Zhang Xue, Wang Yueyin, Huang Huimin, Sharma Shishir, Sharma Sangeeta Shrestha, Wolf Clemens Alexander, Liu Sijie, Wolber Gerhard, Sorensen Erik J, Bureik Matthias
School of Pharmaceutical Science and Technology, Tianjin University, Tianjin, 300072, China.
Pharmaceutical and Medicinal Chemistry (Computer-Aided Drug Design), Institute of Pharmacy, Freie Universität Berlin, 14195, Berlin, Germany.
Appl Biochem Biotechnol. 2023 Feb;195(2):1042-1058. doi: 10.1007/s12010-022-04184-0. Epub 2022 Oct 26.
We report the synthesis of 21 new proluciferin compounds that bear a small aliphatic ether group connected to the 6' hydroxy function of firefly luciferin and either contain an acid or methyl ester function at the dihydrothiazole ring. Each of these compounds was found to be a substrate for some members of the human CYP1 and CYP3 families; a total of 92 new enzyme-substrate pairs were identified. In a screen of the whole human P450 complement (CYPome) with three selected proluciferin acid substrates, another 13 enzyme-substrate pairs were detected, which involve enzymes belonging to the CYP2, CYP4, CYP7, CYP21, and CYP27 families. All in all, we identified new probe substrates for members of seven out of 18 human CYP families.
我们报告了21种新的荧光素前体化合物的合成，这些化合物带有一个连接到萤火虫荧光素6'羟基官能团的小脂肪族醚基团，并且在二氢噻唑环上含有一个酸或甲酯官能团。发现这些化合物中的每一种都是人类CYP1和CYP3家族某些成员的底物；总共鉴定出92对新的酶-底物对。在用三种选定的荧光素前体酸底物对整个人类P450补体（CYPome）进行的筛选中，又检测到另外13对酶-底物对，它们涉及属于CYP2、CYP4、CYP7、CYP21和CYP27家族的酶。总而言之，我们为18个人类CYP家族中的7个家族的成员鉴定了新的探针底物。
