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Targeting DNA with triplexes

Targeting DNA with triplexes
Targeting DNA with triplexes
The formation of intermolecular DNA triple helices offers the possibility of designing compounds with extensive sequence recognition properties which may be useful as antigene agents or tools in molecular biology. In these structures a third strand oligonucleotide binds in the DNA major groove, making specific contacts with substituents on the exposed faces of the base pairs. Although triplexes form with exquisite specificity their use suffers from several drawbacks. Two limitations of this approach, which are considered in this review are, firstly that conditions of low pH are necessary for formation of the C +l GC triplet, and secondly that these structures are often less stable than their duplex counterparts. This review outlines the strategies that have been employed to overcome these drawbacks. The pH problem is addressed by considering the various DNA base analogues that have been used to recognise GC base pairs in a pH independent fashion, and discusses the benefits and limitations of each analogue. Triplex stability can be increased by using novel base analogues, backbone modifications and the use of triplex-specific binding ligands.
triplexes, intermolecular dna triple elices, antigene agents, dna helix, sequence recognition, rna triple helices, cytosine protonation, purine analogues, pyrimidine analogues, base stacking, spermine, phosphorothioates, methylphosphonates, modified dna sugars, naphthylquinoline derivatives, tethered dna binding agents, intercalators, tethered triplex binding ligands, antiparallel triplexes, self association, g rich oligonucleotides
0929-8673
17-37
Fox, K.R.
9da5debc-4e45-473e-ab8c-550d1104659f
Fox, K.R.
9da5debc-4e45-473e-ab8c-550d1104659f

Fox, K.R. (2000) Targeting DNA with triplexes. Current Medicinal Chemistry, 7 (1), 17-37.

Record type: Article

Abstract

The formation of intermolecular DNA triple helices offers the possibility of designing compounds with extensive sequence recognition properties which may be useful as antigene agents or tools in molecular biology. In these structures a third strand oligonucleotide binds in the DNA major groove, making specific contacts with substituents on the exposed faces of the base pairs. Although triplexes form with exquisite specificity their use suffers from several drawbacks. Two limitations of this approach, which are considered in this review are, firstly that conditions of low pH are necessary for formation of the C +l GC triplet, and secondly that these structures are often less stable than their duplex counterparts. This review outlines the strategies that have been employed to overcome these drawbacks. The pH problem is addressed by considering the various DNA base analogues that have been used to recognise GC base pairs in a pH independent fashion, and discusses the benefits and limitations of each analogue. Triplex stability can be increased by using novel base analogues, backbone modifications and the use of triplex-specific binding ligands.

Full text not available from this repository.

More information

Published date: January 2000
Keywords: triplexes, intermolecular dna triple elices, antigene agents, dna helix, sequence recognition, rna triple helices, cytosine protonation, purine analogues, pyrimidine analogues, base stacking, spermine, phosphorothioates, methylphosphonates, modified dna sugars, naphthylquinoline derivatives, tethered dna binding agents, intercalators, tethered triplex binding ligands, antiparallel triplexes, self association, g rich oligonucleotides

Identifiers

Local EPrints ID: 56383
URI: https://eprints.soton.ac.uk/id/eprint/56383
ISSN: 0929-8673
PURE UUID: 397a8ffc-c1c7-490c-be28-74f318aa2268
ORCID for K.R. Fox: ORCID iD orcid.org/0000-0002-2925-7315

Catalogue record

Date deposited: 07 Aug 2008
Last modified: 14 Mar 2019 01:56

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