Assembly of an Antiparallel Homo-Adenine DNA Duplex by Small-Molecule Binding

Molecules that reversibly bind DNA and trigger the formation of non-Watson−Crick secondary structures would be useful in the design of dynamic DNA nanostructures and as potential leads for new therapeutic agents. We demonstrate that coralyne, a small crescent-shaped molecule, promotes the formation of a duplex secondary structure from homo-adenine oligonucleotides. AFM studies reveal that the staggered alignment of homo-adenine oligonucleotides upon coralyne binding produces polymers of micrometers in length, but only 2 nm in height. A DNA duplex was also studied that contained eight A·A mismatches between two flanking 7-bp Watson−Crick helices. CD spectra confirm that the multiple A·A mismatches of this duplex bind coralyne in manner similar to that of homo-adenine oligonucleotides. Furthermore, the melting temperature of this hybrid duplex increases by 13 °C upon coralyne binding. These observations illustrate that the helical structure of the homo-adenine−coralyne duplex is compatible with the B-form DNA helix.