Calorimetric, spectroscopic and computational investigation of DNA triplexes containing a 3 '-3 ' internucleoside junction

Triple helix (triplex) formation between a 24-mer oligonucleotide double he lix (duplex) and two kinds of 24-mer single strands containing a 3'-3' phos phodiester bond was investigated by calorimetric, spectroscopic and computa tional techniques in order to analyze the effect of chemical modification o f the third strand on the stability of DNA triplex. The duplex target is co mposed of two adjacent oligopurine-oligopyrimidine domains where the oligop urine sequences alternate on the two duplex strands. The third strands diff er between each other from the substitution of cytosine with a thymine at t he junction point. The two triplexes exhibit different CD spectra, suggesti ng that they have non-equivalent conformational states. Differential scanni ng calorimetric data show that the triplex with a cytosine-thymine junction (CT-triplex) is thermodynamically less stable than that with a cytosine-cy tosine junction (CC-triplex). Molecular mechanics calculations revealed tha t the two triplexes have different geometries at the junction point. The th ermodynamic data are successfully discussed in relation to the molecular mo dels of the two triplexes.