Abstract
DNA structures with parallel strand alignment can be formed from oligonucleotides containing exclusively AT base pairs. Intramolecular duplexes, containing polarity reversal 5’-5’ phosphodiester linkages, and intermolecular duplex DNA containing either homo-oligomeric or alternating A-T sequences can exist in vitro as parallel-stranded (PS) DNA. The formation of stable PS duplex structures is demonstrated by the following criteria: (i) electrophoretic mobilities under native conditions are similar to those of antiparallel-stranded (APS) duplexes. (ii) spectroscopic properties are characteristic for base paired structures but are different from those of the corresponding APS duplex. (iii) PS duplexes undergo thermally induced helix to coil transitions, however, the melting temperature is considerably lower than that of APS DNA. (iv) NMR measurements support a normal phosphodiester backbone conformation for PS DNA as well as base pairing and base stacking between T and A residues similar to those in APS DNA. Ethidium bromide binds more strongly to parallel stranded DNA with a higher fluorescence quantum yield than that for the binding to APS DNA. In contrast, the minor groove specific ligand Hoechst 33258 exhibits a markedly reduced affinity for PS DNA compared to the binding of this drug to control APS duplex DNA. The reverse Watson-Crick base pairing between the T and A residues of parallel stranded DNA results in the presence of the 5-CH3 group in the minor groove of the DNA which could sterically inhibit the binding of ligands such as Hoechst 33258.
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