Oxidative activation of leinamycin E1 triggers alkylation of guanine residues in double-stranded DNAElectronic supplementary information (ESI) available. See DOI: 10.1039/c7cc08482j

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...

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Bibliographic Details
Main Authors: Imani Nejad, Maryam, Yang, Dong, Shen, Ben, Gates, Kent S
Format: Article
Language:English
Online Access:Get full text
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Summary: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 H 2 O 2 and other byproducts of cellular oxidative stress initiates generation of an episulfonium ion that selectively alkylates guanine residues in duplex DNA. It may be useful to develop prodrugs that are selectively activated by oxidative stress in cancer cells to release cell-killing reactive intermediates.
ISSN:1359-7345
1364-548X
DOI:10.1039/c7cc08482j