X-RAY CRYSTAL-STRUCTURE OF A DIMETHYLENE SULFONE-BRIDGED RIBONUCLEOTIDE DIMER IN A SINGLE-STRANDED STATE

A crystal structure has been solved for an analog of the r(ApU) ribodi nucleotide, r(Aso(2)U), where a bridging non-ionic dimethylene sulfone linker replaces the phosphodiester linking group found in natural RNA , Crystals of the single-stranded state of r(Aso(2)U) were obtained fr om water at 50 degrees C, In these crystals, one hydrogen bond is form ed between bases from different strands and base stacking occurs in in termolecular 'home-A' and 'homo-U' stacks, Similar to typical oligorib onucleotides, the ribose rings adopt N-type conformations and dihedral angles chi are in the anti range, The all-trans rotamer of the CH2-SO 2-CH2-CH2 bridge was found, which leads to a large adenine-uracil dist ance, Qualitative analysis of a NOESY spectrum of the Aso(2)U part in r(Uso(2)Cso(2)Aso(2)U) dissolved in a dimethylsulfoxide-D2O mixture in dicates that the conformation observed in the crystal is also populate d in solution, Comparison with the structure of r(Gso(2)C), which has been crystallized in the Watson-Crick paired state, shows that a rotat ion around zeta by +112 degrees leads from the observed, single-strand ed state to a conformation that is compatible with formation of a dupl ex, A concerted translgauche flip of alpha and gamma then yields the s tandard conformer of A-type RNA helices, From the observed structure o f r(Gso(2)C) and other oligonucleotides it is anticipated that this fl ip will also revert the ribose pucker from C2'-exo to C3'-endo.