The intrinsic structure and stability of out-of-alternation base pairs in Z-DNA

Alternating pyrimidine-purine sequences typically form Z-DNA, with the pyri midines in the anti and purines in the syn conformations. The observation t hat dC and dT nucleotides can also adopt the syn conformation (i,e, the nuc leotides are out-of-alternation) extends the range of sequences that can co nvert to this left-handed form of DNA, Here, we study the effects of placin g two adjacent d(G.C) base pairs as opposed to a single d(G.C) base pair or two d(A.T) base pairs out-of-alternation by comparing the structure of d(m (5)CGGCm(5)CG)(2) with the previously published structures of d(m(5)CGGG(5) m(5)CG).d(m(5)CGCCm(5)CG) and d(m(5)CGATm(5)CG)(2). A high buckle and loss of stacking interactions are observed as intrinsic properties of the out-of -alternation base pairs regardless of sequence and the context of the dinuc leotide, From solution titrations, we find that the destabilizing effect of out-of-alternation d(G.C) base pairs are identical whether these base pair s are adjacent or isolated. We can therefore conclude that it is these intr insic distortions in the structure of the base pairs and not neighboring ef fects that account for the inability of out-of-alternation base pairs to ad opt the left-handed Z conformation.