发现并利用氧化酶进行抗癌喜树碱类似物的化学酶促合成及多样化修饰。
Discovering and harnessing oxidative enzymes for chemoenzymatic synthesis and diversification of anticancer camptothecin analogues.
作者信息
Nguyen Tuan-Anh M, Nguyen Trinh-Don, Leung Yuen Yee, McConnachie Matthew, Sannikov Oleg, Xia Zhicheng, Dang Thu-Thuy T
机构信息
Irving K. Barber Faculty of Science, Department of Chemistry, University of British Columbia, 3427 University Way, Kelowna, BC, V1V 1V7, Canada.
Faculty of Science, Department of Chemistry, University of British Columbia, 2036 Main Mall, Vancouver, BC, V6T 1Z1, Canada.
出版信息
Commun Chem. 2021 Dec 16;4(1):177. doi: 10.1038/s42004-021-00602-2.
Semi-synthetic derivatives of camptothecin, a quinoline alkaloid found in the Camptotheca acuminata tree, are potent anticancer agents. Here we discovered two C. acuminata cytochrome P450 monooxygenases that catalyze regio-specific 10- and 11-oxidations of camptothecin, and demonstrated combinatorial chemoenzymatic C-H functionalizations of the camptothecin scaffold using the new enzymes to produce a suite of anticancer drugs, including topotecan (Hycamtin®) and irinotecan (Camptosar®). This work sheds new light into camptothecin metabolism, and represents greener approaches for accessing clinically relevant camptothecin derivatives.
喜树碱是从喜树中发现的一种喹啉生物碱，其半合成衍生物是强效抗癌剂。在此，我们发现了两种喜树细胞色素P450单加氧酶，它们催化喜树碱的区域特异性10位和11位氧化，并利用这些新酶对喜树碱骨架进行组合化学酶促C-H官能化反应，以生产一系列抗癌药物，包括拓扑替康（Hycamtin®）和伊立替康（Camptosar®）。这项工作为喜树碱的代谢研究提供了新线索，也代表了获取临床相关喜树碱衍生物的更绿色方法。
Zotero 插件