Optimization of Hammerhead Flanking Sequences Using Oligonucleotide Facilitators

The ability to catalyze selected chemical reactions could be of great theoretical and practical value. Uhlenbeck first demonstrated a general method to design catalysts that could distinguish the intended substrates from other, very similar molecules (1 ). The reaction catalyzed was phosphodrester exchange within the backbone of an RNA that led to chain cleavage at the site of reaction. Activity was achieved by generating the “hammerhead” structural motif found in certain self-cleaving RNA molecules (2 ), and selectivity resulted from appropriate Watson-Crick base pairing between the catalyst and its substrate.