What Makes a Triple Helix Useful in Drug Design?
Triple-helical DNA was first observed in 1957 in the course of an investigation of synthetic polynucleotides, but for decades it remained a laboratory curiosity. Recent studies have shown that synthetic oligonucleotides (usually about 15 nucleotide residues long) bind to specific sequences of naturally occurring double-helical DNA. The oligonucleotides are chemically synthesized to have the correct base sequence for specific binding. The oligonucleotide that forms the third strand fits into the major groove of the double helix and forms specific hydrogen bonds.
When the third strand is in place, the major groove is inaccessible to proteins that might otherwise bind to that site-specifically, proteins that activate or repress expression of that portion of DNA as a gene. This behavior suggests a possible in vivo role for triple helices, especially in view of the fact that hybrid triplexes with a short RNA strand bound to a DNA double helix are particularly stable.
In another aspect of this work, researchers who have studied triple helices have synthesized oligonucleotides with reactive sites that can be positioned in definite places in DNA sequences. Such a reactive site can be used to modify or cleave DNA at a chosen point in a given sequence. This kind of specific cutting of DNA is crucial to recombinant DNA technology and to genetic engineering.