TARGETING NUCLEIC ACIDS IN BACTERIA WITH SYNTHETIC LIGANDS

Abbas Nikravesh (Thesis for doctoral degree (Ph.D.))         
Stockholm 2008
From the Programme for Genomics and Bioinformatics
Department of Cell and Molecular Biology
Karolinska Institutet, Stockholm, Sweden



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3.4 PAPER IV
Friedreich’s ataxia (GAA)n triplex DNA structures are stabilized by Benzoquinoquinoxaline derivatives

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5 FUTURE PERSPECTIVES
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The experiments on (GAA)n repeat sequences described in this thesis were restricted to in vitro studies and probing of E. coli plasmid DNA. Nevertheless, the evidence that we provide for the existence of triplex structures within FA (GAA)n repeats suggests that destabilization of these structures could provide a possible therapeutic strategy for patients. Whereas BQQ stabilizes triplex structures, other DNA ligands may destabilize triplex structures. Such strategies may offer hope for developing small molecule DNA ligands to treat FA or other conditions that involve triplex DNA structures that arise from tri nucleotide repeat expansions.

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Structure-Specific Recognition of Friedreich's Ataxia (GAA)n Repeats by Benzoquinoquinoxaline Derivatives

ChemBioChem, Published Online: 10 Sep 2009

Helen Bergquist 1, Abbas Nikravesh, Dr. 2, Raquel Domingo Fernández 1, Veronica Larsson 1, Chi-Hung Nguyen, Dr. 3, Liam Good, Dr. 2 4, Rula Zain, Dr. 1 *


1Department of Molecular Biology and Functional Genomics, Stockholm University, Svante Arrhenius väg 20C, 10691 Stockholm (Sweden), Fax: (+46) 8-166488

2Department of Cell and Molecular Biology, Karolinska Institutet, Berzelius väg 35, 17177 Stockholm (Sweden)

3UMR176 CNRS-Institut Curie, Laboratoire de Pharmacochimie, Centre Universitaire, Bâtiment 110, 91405 Orsay (France)

4Department of Pathology and Infectious Diseases, Royal Veterinary College, University of London, Hawkshead Lane, N. Mymms AL9 7TA (UK)