DNA Recognition by Parallel Triplex Formation

Keith R. Fox, Tom Brown and David A. Rusling. DNA-targeting Molecules as Therapeutic Agents 1-32, 2018.


Triplex-forming oligonucleotides (TFOs) are sequence-specific DNA-recognition agents that bind within the duplex major groove by forming Hoogsteen hydrogen bonds with exposed groups on the base pairs, generating a triple-helical, or triplex, structure. The unique recognition properties of these molecules have been exploited in such diverse areas as gene-targeting, diagnostics and bionanotechnology. However, the applications of TFOs containing natural nucleotides is somewhat restricted by their low affinity and slow association kinetics at physiological pH, as well as a requirement for oligopurine–oligopyrimidine duplex target sequences. In recent years these limitations have been overcome by using TFOs incorporating novel base, sugar and backbone modifications, and triplex formation at mixed sequence duplex targets with high affinity at physiological pH is now achievable. This review will discuss the structural properties and solution requirements of DNA triplexes, with reference to state-of-the-art of modifications used to improve the DNA-recognition properties of TFOs.