Joining of multiple duplex stems at a single quadruplex loop.

We report here the formation of stable DNA quadruplex-duplex hybrid complexes harboring multiple duplex stems within the same loop of a quadruplex structure. The folding topology of a two-stem quadruplex-duplex hybrid construct was validated using nuclear magnetic resonance (NMR) spectroscopy. This multi-stem incorporation principle is applicable at different loop positions of the same quadruplex construct and could be extended to three or more duplex stems, giving rise to a diverse range of possible structures. These multi-stem complexes offer new design principles for the assembly of DNA architectures. The potential existence of such complex motifs in genomic sequences could have biological implications and would represent novel targets for drug development.