Tripelhelices

Tripelhelices, or triplex helices, are nucleic acid structures in which a third strand binds to a standard DNA duplex to form a three-stranded helix. The third strand associates in the major groove of the duplex through Hoogsteen or reverse Hoogsteen hydrogen bonds, generating triplet base pairs such as C+·G-C, T·A-T, or A·T-A depending on sequence and geometry. Most naturally observed in DNA segments rich in purines on one strand, triplex formation can occur under specific conditions and is influenced by pH, ionic strength, and chromatin context.

Two principal motifs are described: a parallel triplex, where the third strand runs in the same direction as one duplex strand and binds through Hoogsteen bonds to the duplex; and an antiparallel triplex, where the third strand runs opposite and uses different pairing schemes. In many systems, triplex formation requires homopurine-homopyrimidine stretches, typically several dozen to a few hundred bases long, and often depends on protonated cytosine residues at lower pH.

Biological relevance and applications: DNA triplexes have been implicated in transcriptional regulation and recombination; they can form in supercoiled DNA and under certain cellular conditions. In biotechnology, triplex-forming oligonucleotides (TFOs) are explored as antigene agents to block transcription or to recruit targeted modifications; limitations include restricted target sequences, reduced stability in vivo, and potential off-target effects. Strategies include chemical modification of TFOs and optimization of binding conditions.

See also: Hoogsteen base pairing; DNA triplex; antigene therapy.