2′-SUBSTITUTED PHOSPHOROTHIOATE CONTAINING OLIGORIBONUCLEOTIDES: AN APPLICATION TO THE SYNTHESIS AND PURIFICATION OF HAMMERHEAD RIBOZYMES

A systematic study of the catalytic activity and nuclease stability of selectively modified hammerhead ribozymes has resulted in the identification of a generic motif containing 5 ribose residues and 31 2′- modified sugars (1). This substructure has been further elaborated to include phosphorothioate linkages. Although oligodeoxyribonucleotides containing phosphorothioate linkages have been studied extensively, similarly substituted RNA molecules or ribozymes have not been explored at-length. The synthesis and purification of these ribozymes is discussed (2).