Metallo-regulation of the bimolecular triplex formation of a peptide nucleic acid

Abstract

Peptide nucleic acid (PNA) conjugates incorporating a bipyridine unit were prepared. The bipyridine was built into the loop moiety of PNAs that were designed to specifically form a hairpin and a PNA/DNA bimolecular triplex. While the thermal stability of the hairpin structure was only minimally affected by Cu²⁺ addition, the PNA/DNA bimolecular triplex structure was significantly destabilized by complexation with Cu²⁺. The melting temperature of the bimolecular triplex decreased by 17.4 °C in the presence of Cu²⁺. This corresponds to more than a 1000 fold decrease in the binding constant for bimolecular triplex formation. Upon complexation, the bipyridine unit underwent a drastic conformational change which accounts for the observed differences in the thermal stabilities of the triplex upon binding. The bipyridine–PNA conjugate may be useful as an allosteric DNA carrier that releases the DNA in response to a certain metal ion concentration.