Targeting DNA with Triplexes
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.
Keywords: DNA helix; G rich oligonucleotides; Purine analogues; RNA triple helices; Tethered DNA binding agents; antigene agents; antiparallel triplexes; base stacking; cytosine protonation; intercalators; intermolecular DNA triple elices; methylphosphonates; modified DNA sugars; naphthylquinoline derivatives; phosphorothioates; pyrimidine analogues; self association; sequence recognition; spermine; tethered triplex binding ligands; triplexes
Document Type: Review Article
Publication date: 2000-01-01
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