Specific DNA oligomers will be synthesized to use a model systems to aid in the understanding of the structure- activity relationship of certain nucleic acid conformations. These model conformations will be examined with high resolutions by employing state of the arts techniques. It has been suggested that Z-DNA may contribute to the control of biological events, in particular, genetic activities. Although direct evidence is still lacking or at least incomplete, the suggestion has not been disproved. Therefore it is very plausible that mechanisms of conformational transition in DNA are best studied on Z-DNA models. In particular, the primary goal of this project is to expand the work already completed on the structural analysis of B-Z junctions. Much of the work will incorporate a B-Z junction into an already well defined system. There are four major areas of interest: 1) multiple and poly conformational junctions; 2) B-Z junctions in DNA hairpins and dumbbells; 3) the effects of base pair mismatches at or near a B-Z junction; and, 4) the hyperactivity of B-Z junctions to certain carcinogens. Multiple and poly junctions will examine the effect of the presence of many conformational junctions on the global conformation of a long DNA oligomer. The effects of the loops in hairpins and dumbbells and the effects of mismatches at or near a junction will be evaluated in terms of the thermodynamics of the DNA duplexes in question. Their effects on the formation and structure of the junction will also be evaluated.
