Triple-helical nucleic acids are formed by binding an oligonucleotide within the major groove of duplex DNA. These complexes offer the possibility of designing oligonucleotides which bind to duplex DNA with considerable sequence specificity. However, triple-helix formation with natural nucleotides is limited by (i) the requirement for low pH, (ii) the requirement for homopurine target sequences, and (iii) their relatively low affinity. We have prepared modified oligonucleotides to overcome these limitations, including the addition of positive charges to the sugar and/or base, the inclusion of cytosine analogues, the development of nucleosides for recognition of pyrimidine interruptions and the attachment of one or more cross-linking groups. By these means we are able to generate triplexes which have high affinities at physiological pH at sequences that contain pyrimidine interruptions.
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April 2011
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Conference Article|
March 22 2011
Formation of stable DNA triplexes
Keith R. Fox;
Keith R. Fox
1
*School of Biological Sciences, Life Science Building 85, University of Southampton, Southampton SO17 1BJ, U.K.
1To whom correspondence should be addressed (email K.R.Fox@soton.ac.uk).
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Tom Brown
Tom Brown
†School of Chemistry, University of Southampton, Southampton SO17 1BJ, U.K.
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Publisher: Portland Press Ltd
Received:
September 06 2010
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© The Authors Journal compilation © 2011 Biochemical Society
2011
Biochem Soc Trans (2011) 39 (2): 629–634.
Article history
Received:
September 06 2010
Citation
Keith R. Fox, Tom Brown; Formation of stable DNA triplexes. Biochem Soc Trans 1 April 2011; 39 (2): 629–634. doi: https://doi.org/10.1042/BST0390629
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