A THYMINE-LIKE BASE ANALOG FORMS WOBBLE PAIRS WITH ADENINE IN A Z-DNADUPLEX

The DNA hexamer d(CACGPG), in which dP is the ambivalent pyrimidine nu cleoside analogue H,8H-3,4-dihydropyrimido[4,5-c][1,2]oxazin-7-one), c rystallises as a left-handed Z-DNA duplex. X-ray analysis at 1.5 Angst rom shows that both PA base-pairs are of the wobble type. This result appears inconsistent with other evidence from hybridisation and NMR st udies of P-containing oligonucleotides, which suggests that, while P c an form stable base-pairs with either A or G, thymine-like properties are more pronounced. Thermal denaturation experiments over a range of solution pH values indicate that protonation of the P A base-pairs is unlikely to be responsible for the anomalous behaviour. No specific cr ystal packing effects can be identfied as an explanation and it is con cluded that base stacking and other interactions between nucleotide re sidues in Z-DNA are responsible. (C) 1998 Academic Press.