Sequence-Specific DNA Alkylation

  • Author: Claire D'Andola
  • Published Date: 15 January 2014
  • Source / Publisher: Chemistry – A European Journal/Wiley-VCH
  • Copyright: Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
thumbnail image: Sequence-Specific DNA Alkylation

Related Societies

DNA mutations and epigenetic modifications are attractive to researchers as important targets for anticancer agents. Anticancer drugs, such as cisplatin, mitomycin C, and chlorambucil, which covalently bond to DNA, are used routinely in cancer treatment. However, the strong toxicity of these drugs induces severe adverse effects.
The introduction of sequence specificity to cancer-induced mutated gene sequences may improve their anticancer activity. Mutation of the Kras gene is a key step in many cancers and one of the most frequently activated oncogenes, with point mutations often occurring at codons 12, 13, and 61, making these mutations attractive targets for potential anticancer drugs.


Toshikazu Bando, Hiroshi Sugiyama, and co-workers, Kyoto University, Japan, have investigated the sequence-specific alkylating activity of polyamide-seco-1,2,9,9a-tetrahydrocyclopropa[1,2-c]benz[1,2-e]indol-4-one (polyamide-seco-CBI) conjugates that alkylated the codon 13 mutation region in the coding region of the Kras gene.
Two of the polyamide-seco-CBI conjugates showed selectivity and alkylated the template strand of the coding region of the codon 13 mutation, with one showing potent specific alkylation activity for the codon 13 mutation, which was more efficient than for the other polyamide conjugates.


This method could be used for specific cancer chemotherapy and may be a promising approach to overcome the problem of drug-resistance and side effects in cancer treatments.


Article Views: 3958

Sign in Area

Please sign in below

Additional Sign In options

Please note that to comment on an article you must be registered and logged in.
Registration is for free, you may already be registered to receive, e.g., the newsletter. When you register on this website, please ensure you view our terms and conditions. All comments are subject to moderation.

Article Comments - To add a comment please sign in

Bookmark and Share

If you would like to reuse any content, in print or online, from ChemistryViews.org, please contact us first for permission. more


CONNECT:

ChemistryViews.org on Facebook

ChemistryViews.org on Twitter ChemistryViews.org on YouTube ChemistryViews.org on LinkedIn Sign up for our free newsletter


Magazine of Chemistry Europe (16 European Chemical Societies)published by Wiley-VCH