We wish to elucidate conformations of DNA in solution, and to investigate their relationships to genetic function, interactions, with drugs, and protein recognition. The method we have chosen to carry out such studies is nuclear magnetic resonance (NMR) spectroscopy; more specifically the method used to detail these solution conformations is the 2D-NOE NMR method, which provides relative interatomic distances. Loops in DNA are expected to be important for protein recognition of selective genetic sites, such as RNA polymerase promotor sequences. Consequently, we have studied quasipalindromic synthetic oligonucleotides and the mechanism of hairpin loop formation. In addition to studies with normal oligos, we are investigating phosphorothioate oligo duplexes by the above NMR methods. This is complicated by the fact that due to non-sterospecific synthesis each thio-phosphate can exist in two sterospecific forms. NMR should help to clarify the conformation(s) of the low temperature duplex form of oligo analogs.
