Nuclear magnetic resonance (NMR) spectroscopy will provide an important probe of the detailed chemical structure and dynamics of nucleic acids (DNA, RNA, tRNA) and nucleic acid complexes. NMR is virtually a unique technique capable of providing an understanding of the chemical basis of genetic diseases and the structural basis for protein, carcinogen, and drug binding to nucleic acids. We have recently proposed that 31P chemical shifts are sensitive to the conformation about phosphate ester bonds. The 31P NMR spectra will thus provide a powerful probe of conformation of nucleic acids and nucleic acid drug and nucleic acid carcinogen complexes. We will consider the 31P NMR spectra of double-helical nucleic acids and, in particular, spectral changes in going from a """"""""B"""""""" DNA to a """"""""Z"""""""" DNA conformation. The latter has been implicated in possible carcinogen activation of genes. Phosphorus NMR spectra of transfer RNA will be used to provide support to the hypothesis that these molecules exist in at least two conformations, which has been suggested to be important in protein biosynthesis. The conformational changes upon lac repressor headpiece binding to a 14 base pair DNA lac operator fragment will be probed by 31P NMR. In the nucleic acid systems all oligonucleotides, thiophosphoryl and 170-phosphoryl) oligonucleotides, and covalently modified oligonucleotides will be chemically synthesized by the phosphoramite method on solid supports.
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