An extra dimension in nucleic acid sequence recognition

Abstract

Introduction 312

Triple helices in DNA 312

Chemically modified TFOs 313

Further development 316

Recognition of GC base pairs 316

Recognition of TA base pairs 316

Recognition of AT base pairs 317

Recognition of CG base pairs 317

RNA triplexes 317

Kinetics of triplex formation 318

Practical applications of triplexes 318

Conclusions 319

References 319

Watson–Crick base pairing is a natural molecular recognition process that has been exploited in molecular biology and universally adopted in many fields. An additional mode of nucleic acid sequence recognition that could be used in combination with normal base pairing would add an exta dimension to nucleic acid interactions and open up many new applications. In principle the triplex approach could provide this if developed to recognize any DNA sequence. To this end modified nucleosides have been incorporated into triple-helix-forming oligonucleotides (TFOs) and used to recognize mixed sequence DNA with high selectivity and affinity at neutral pH. Continuing developments are directed towards improving TFO affinity at high pH and increasing triplex association kinetics. A number of applications of triplexes are currently being explored.