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Formation of stable DNA triplexes

Formation of stable DNA triplexes
Formation of stable DNA triplexes
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.

0300-5127
629-634
Fox, Keith R.
9da5debc-4e45-473e-ab8c-550d1104659f
Brown, Tom
a64aae36-bb30-42df-88a2-11be394e8c89
Fox, Keith R.
9da5debc-4e45-473e-ab8c-550d1104659f
Brown, Tom
a64aae36-bb30-42df-88a2-11be394e8c89

Fox, Keith R. and Brown, Tom (2011) Formation of stable DNA triplexes. Biochemical Society Transactions, 39 (2), 629-634. (doi:10.1042/BST0390629).

Record type: Article

Abstract

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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More information

Published date: 2011
Venue - Dates: nacon VIII: 8th International Meeting on Recognition Studies in Nucleic Acids, 2011-01-01
Organisations: Molecular and Cellular

Identifiers

Local EPrints ID: 206539
URI: http://eprints.soton.ac.uk/id/eprint/206539
ISSN: 0300-5127
PURE UUID: 7d376a3a-0615-4181-8481-542225cf7dc3
ORCID for Keith R. Fox: ORCID iD orcid.org/0000-0002-2925-7315

Catalogue record

Date deposited: 22 Dec 2011 16:39
Last modified: 15 Mar 2024 02:36

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