STRUCTURE AND DYNAMICS OF MMI-LINKED NUCLEOTIDES

Results are presented on molecular dynamics (MD) simulations of (TT) dimers linked by a novel chemical functionality - the methylene methyl imino (MMI) backbone designed as a neutral replacement for the negati vely charged phosphodiester group in wild type nucleic acids. Simultan eous conformational transitions among the MMI backbone atoms during th e course of the simulation have been observed, equivalent to inversion -rotation at the nitrogen atoms of the N-O bond. This process yields t wo families of low-energy conformations which maintain base stacking. The solution structure of the dimer has been studied by one and two-di mensional H-1 NMR spectroscopy, and two slowly exchanging forms are ob served at low temperature. Simulated NOESY spectra generated from the MD structures match the experimental NOESY data.