Distamycin-stabilized antiparallel-parallel combination (APC) DNA

The formation of Antiparallel-Parallel-Combination (APC) DNA, a liner duplex with a segment of parallel-stranded (ps) helix flanked by conventional B-DNA, was tested with a number of synthetic oligonucleotides. The groove-binding ligand distamycin A (DstA) was used to stabilize the ps segment comprising five A x T base pairs. Two drug molecules bound per APC, one in each of the two equivalent grooves characteristic of ps-DNA. APC-DNA, reference molecules and their complexes with DstA were analysed by several methods: circular dichroism and absorption spectroscopy, thermal denaturation, chemical modification, and molecular modeling. The dye binding stoichiometry differed significantly due to inherent structural differences in the groove geometries of ps-DNA (trans base pairs, similar grooves) and conventional antiparallel-stranded (aps) B-DNA (cis base pairs, distinct major and minor grooves). The data support the existence of APC folding in solution.