The introduction of a North-type sugar conformation constrained oxetane T block, 1-(1',3'-O-anhydro-β-D-psicofuranosyl) thymine, at the T⁷ position of the self-complementary Dickerson-Drew dodecamer, d[(5'-C¹G²C³G⁴A⁵A⁶T⁷T⁸C⁹G¹⁰C¹¹G¹²-3')]₂, considerably perturbs the conformation of the four central base pairs, reducing the stability of the structure. UV spectroscopy and 1D NMR display a drop in melting temperature of ∼10 °C per modification for the T⁷ oxetane modified duplex, where the T⁷ block has been introduced in both strands, compared to the native Dickerson-Drew dodecamer. The three dimensional structure has been determined by NMR spectroscopy and has subsequently been compared with the results of 2.4 ns MD simulations of the native and the T⁷ oxetane modified duplexes. The modified T⁷ residue is found to maintain its constrained sugar- and the related glycosyl torsion conformations in the duplex, resulting in staggered and stretched T⁷·A⁶ and A⁶·T⁷ non-linear base pairs. The stacking is less perturbed, but there is an increased roll between the two central residues compared to the native counterpart, which is compensated by tilts of the neighboring base steps. The one dimensional melting profile of base protons of the T⁷ and T⁸ residues reveals that the introduction of the North-type sugar constrained thymine destabilizes the core of the modified duplex, promoting melting to start simultaneously from the center as well as from the ends. Temperature dependent hydration studies by NMR demonstrate that the central T⁷·A⁶/A⁶·T⁷ base pairs of the T⁷ oxetane modified Dickerson-Drew dodecamer have at least one order of magnitude higher water exchange rates (correlated to the opening rate of the base pair) than the corresponding base pairs in the native duplex.