Issue 3, 2018

Oxidative activation of leinamycin E1 triggers alkylation of guanine residues in double-stranded DNA

Abstract

It may be useful to develop prodrugs that are selectively activated by oxidative stress in cancer cells to release cell-killing reactive intermediates. However, relatively few chemical strategies exist for the activation of prodrugs under conditions of oxidative stress. Here we provide evidence for a novel process in which oxidation of a thiol residue in the natural product leinamycin E1 by H2O2 and other byproducts of cellular oxidative stress initiates generation of an episulfonium ion that selectively alkylates guanine residues in duplex DNA.

Graphical abstract: Oxidative activation of leinamycin E1 triggers alkylation of guanine residues in double-stranded DNA

Supplementary files

Article information

Article type
Communication
Submitted
06 Nov. 2017
Accepted
01 Dec. 2017
First published
05 Dec. 2017

Chem. Commun., 2018,54, 256-259

Oxidative activation of leinamycin E1 triggers alkylation of guanine residues in double-stranded DNA

M. Imani Nejad, D. Yang, B. Shen and K. S. Gates, Chem. Commun., 2018, 54, 256 DOI: 10.1039/C7CC08482J

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