Synthesis and Properties of Non-Hammerhead RNA Using 1-(2-Chloroethoxy)-ethyl Group for the Protection of 2'-Hydroxyl Function

The new type protecting group, 1- (2-chloroethoxy)ethyl (Cee) group has been employed for the protection of the 2'-hydroxyl functions of ribonucleoside residues in the synthesis of oligoribonucleotides by the phosphoramidite approach on a solid support, using an acid-labile 5'-dimethoxytrityl group. This group is completely stable under the acidic conditions required to remove the 5'-terminal protecting groups in oligonucleotide synthesis on a solid support, and yet is easily removable under the similar conditions to that of the tetrahydropyranyl (Thp) in the region of pH 2-3 for the final unblocking step. The synthesis of the Cee-protected ribonucleoside 3'-phosphoramidite units proceed smoothly. The Cee-protected ribnucleoside 3'-phosphoramidite units were evaluated in the synthesis of oligoribonucleotides of up to 20 mer residues. The autocleavage of a precursor RNA from bacteriophage T4 (p2Sp1 RNA; precursor of species 1) does not contain the "hammerhead" sequence required for the authocleavage of other known self-cleaving RNA.