Neumann Kevin, Gambardella Alessia, Lilienkampf Annamaria, Bradley Mark
EaStCHEM School of Chemistry , University of Edinburgh , Joseph Black Building, King's Buildings, David Brewster Road , EH9 3FJ Edinburgh , UK . Email:
Chem Sci. 2018 Jul 12;9(36):7198-7203. doi: 10.1039/c8sc02610f. eCollection 2018 Sep 28.
The selective and biocompatible activation of prodrugs within complex biological systems remains a key challenge in medical chemistry and chemical biology. Herein we report, for the first time, a dual prodrug activation strategy that fully satisfies the principle of bioorthogonality by the symbiotic formation of two active drugs. This dual and traceless prodrug activation strategy takes advantage of the DA chemistry of tetrazines (here a prodrug), generating a pyridazine-based miR21 inhibitor and the anti-cancer drug camptothecin and offers a new concept in prodrug activation.
在复杂生物系统中实现前药的选择性和生物相容性激活仍然是药物化学和化学生物学中的一项关键挑战。在此，我们首次报道了一种双前药激活策略，该策略通过两种活性药物的共生形成，完全满足生物正交性原理。这种双重且无痕的前药激活策略利用了四嗪（此处为一种前药）的DA化学性质，生成了一种基于哒嗪的miR21抑制剂和抗癌药物喜树碱，并为前药激活提供了一个新概念。
