Figure 1. Assembly of four guanine (G) nucleobases into a quadruplex. The potassium ion in the center stabilizes the structure by bonding to the oxygen atoms on each guanine.
Figure 2. Chemical structures of DNA, RNA and PNA.
A team of investigators at Carnegie Mellon University has formed the first hybrid quadruplex of peptide nucleic acids, or PNAs, with DNA, the genetic code. This result opens new opportunities to study the activity of genetic regions occupied by recently described quadruplex DNA structures, as well as providing a new compound that could be used as a biosensor or to block gene activity associated with diseases such as cancer. The research results, published online, will appear in a forthcoming issue of the Journal of the American Chemical Society.
"PNA2-DNA2 hybrid quadruplexes are extremely stable, suggesting that if we use PNAs to bind with DNA quadruplexes that regulate gene expression, we could prevent disease processes in which these DNA quadruplexes appear to play a role," says Bruce Armitage, Ph.D., associate professor of chemistry at Carnegie Mellon. "PNAs also could be converted into biosensors by coupling them with fluorescent tags that would allow the PNA to report the presence of a successful hybridization to quadruplex-forming sequences either in the genome or in messenger RNA molecules."
"In addition to a new high-affinity DNA recognition mechanism and expanding the scope of molecular recognition by PNA, the PNA2-DNA2 hybrid quadruplex is the first example of homologous hybridization," adds Armitage.
Lauren Ward | EurekAlert!
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