Parallel-stranded duplex DNA containing dA · dU base pairs

Abstract

DNA oligonucleotides with dA and dU residues can form duplexes with trans d(A.U) base pairing and the sugar-phosphate backbone in a parallel-stranded orientation, as previously established for oligonucleotides with d(A.T) base pairs. The properties of such parallel-stranded DNA (ps-DNA) 25-mer duplexes have been characterized by absorption (uv), CD, ir, and fluorescence spectroscopy, as well as by nuclease sensitivity. Comparisons were made with duplex molecules containing (a) dT in both strands, (b) dU in one strand and dT in the second, and (c) the same base combinations in reference antiparallel-stranded (aps) structures. Thermodynamic analysis revealed that total replacement of deoxythymine by deoxyuridine was accompanied by destabilization of the ps-helix (reduction in Tm by -13 degrees C in 2 mM MgCl2, 10 mM Na-cacodylate). The U-containing ps-helix (U1.U2) also melted 14 degrees C lower than the corresponding aps-helix under the same ionic conditions; this difference was very close to that observed between ps and aps duplexes with d(A.T) base pairs. Force field minimized structures of the various ps and aps duplexes with either d(A.T) or d(A.U) base pairs ps/aps and dT/dU combinations are presented. The energy-minimized helical parameters did not differ significantly between the DNAs containing dT and dU.