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Therapeutic Agents Based on DNA Sequence Specific Binding

[ Vol. 15 , Issue. 14 ]

Author(s):

Luke Pett, John A. Hartley and Konstantinos Kiakos   Pages 1293 - 1322 ( 30 )

Abstract:


DNA interactive agents have been used in the clinical setting for the treatment of cancer since the beginning of modern-era chemotherapy. Despite a shift of focus towards molecular targeted therapy, DNA remains a critical macromolecular target for anti-cancer intervention and the next generation of agents must conform to the optimum combination of increased therapeutic activity and reduced off-target toxicity. We evaluate the potential of non-covalent DNA binding small molecules as “gene-control” agents, exploiting inherent or engineered sequence selectivity, to target critical genomic sequences. In addition we review examples of natural products and synthetic derivatives that exert their activity through sequence specific DNA-covalent modification.

Keywords:

Alkylating agents, Anticancer chemotherapeutics, Covalent binding, DNA recognition, DNA-targeting agents, Non-covalent binding, Polyamides, Sequence specificity.

Affiliation:

Cancer Research UK Drug- DNA Interactions Research Group, UCL Cancer Institute, Paul O’Gorman Building, 72 Huntley Street, London, WC1E 6BT, UK.

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