An extra dimension in nucleic acid sequence recognition

Abstract

Introduction 312Triple helices in DNA 312Chemically modified TFOs 313Further development 316Recognition of GC base pairs 316Recognition of TA base pairs 316Recognition of AT base pairs 317Recognition of CG base pairs 317RNA triplexes 317Kinetics of triplex formation 318Practical applications of triplexes 318Conclusions 319References 319Watson–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.