Lookup NU author(s): Dr Gunther Ross,
Dr Paul Smith,
Professor Doug Turnbull,
Professor Robert Lightowlers
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Mutations in mitochondrial DNA (mtDNA) cause a variety of human pathologies. In many patients, mutated and wild-type mtDNAs coexist in the same cell, a situation termed mtDNA heteroplasmy. In the absence of standard therapies for these disorders, a genetic strategy for treatment has been proposed whereby replication of mutated mtDNA is inhibited by the selective hybridization of a nucleic acid derivative, allowing propagation of the wild-type genome and correction of the associated defects. To allow for selective binding under physiological conditions, peptide nucleic acids (PNA) are being used. Two other problems, however, have to be resolved: mitochondrial import and attachment of the PNA to the target DNA to inhibit replication. Mitochondrial localization can be achieved by the addition of a caged lipophilic cation and addition of a photo-cross-linking reagent should facilitate covalent attachment. We therefore report the synthesis of benzophenone-PNA derivatives carrying a triphenylphosphonium moiety and demonstrate irreversible binding selectivity between two DNA molecules that differ by a single nucleotide.
Author(s): Ross GF, Smith PM, McGregor A, Turnbull DM, Lightowlers RN
Publication type: Article
Publication status: Published
Journal: Bioconjugate Chemistry
Print publication date: 01/09/2003
ISSN (print): 1043-1802
ISSN (electronic): 1520-4812
Publisher: American Chemical Society
PubMed id: 13129399
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