HIGH-RESOLUTION MOLECULAR DISCRIMINATION BY RNA

Species of RNA that bind with high affinity and specificity to the bro nchodilator theophylline were identified by selection from an oligonuc leotide library. One RNA molecule binds to theophylline with a dissoci ation constant K-d of 0.1 mu M. This binding affinity is 10,000-fold g reater than the RNA molecule's affinity for caffeine, which differs fr om theophylline only by a methyl group at nitrogen atom N-7. Analysis by nuclear magnetic resonance indicates that this RNA molecule undergo es a significant change in its conformation or dynamics upon theophyll ine binding. Binding studies of compounds chemically related to theoph ylline have revealed structural features required for the observed bin ding specificity. These results demonstrate the ability of RNA molecul es to exhibit an extremely high degree of ligand recognition and discr imination.