Distance Dependent Interhelical Couplings of Organic Rods Incorporated in DNA 4-Helix Bundles

The synthesis of a conjugated linear organic module containing terminal salicylaldehyde groups and a central activated ester, designed for conjugation to amino-modified oligonucleotides, is presented. The organic module has a phenylene−ethynylene backbone and is highly fluorescent. It is conjugated to oligonucleotide sequences and incorporated into specific locations in a well-defined DNA 4-helix bundle (4-HB). The DNA-nanostructure offers precise location control of the organic modules which allows for selective interhelical coupling reactions. In this study, metal-salen formation as well as dihydrazone formation are used to covalently interlink the organic modules. Both coupling reactions are highly dependent on the distances between the organic modules in the 4-HB. Neighboring modules dimerize easier, whereas more distanced modules are less prone to react, even when the linkers are extended. The dimeric products are characterized by denaturing polyacrylamide gel electrophoresis (PAGE), high performance liquid chromatography (HPLC), and matrix assisted laser desorption/absorption ionization time-of-flight (MALDI TOF) mass spectrometry.