High-Resolution Molecular Discrimination by RNA

• Published in: Science (American Association for the Advancement of Science) Vol. 263; no. 5152; pp. 1425 - 1429
• Main Authors: Jenison, Robert D., Gill, Stanley C., Pardi, Arthur, Polisky, Barry
• Format: Journal Article
• Language: English
• Published: Washington, DC American Society for the Advancement of Science 11.03.1994; American Association for the Advancement of Science; The American Association for the Advancement of Science
• Subjects: Analytical biochemistry: general aspects, technics, instrumentation; Analytical, structural and metabolic biochemistry; Base Sequence; Binding Sites; Binding, Competitive; Biochemistry; Biological and medical sciences; Chemical bases; DNA; DNA, Complementary - chemistry; Electric potential; Fundamental and applied biological sciences. Psychology; Hydrogen Bonding; Ligands; Magnetic Resonance Spectroscopy; Molecular Sequence Data; Molecular Structure; Molecules; Nucleic Acid Conformation; Oligonucleotides; Protons; Pumps; Ribonucleic acid; RNA; RNA - chemistry; RNA - metabolism; Sequence Analysis, DNA; Theophylline - chemistry; Theophylline - metabolism; Xanthines; Xanthines - chemistry; Xanthines - metabolism; Alkaloid; Specificity; RNA; Selection; Theophyllin; Affinity; Molecular interaction; Xanthine derivatives; Method; Recognition; Caffeine
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.7510417

Species of RNA that bind with high affinity and specificity to the bronchodilator theophylline were identified by selection from an oligonucleotide library. One RNA molecule binds to theophylline with a dissociation constant K$_d$ of 0.1 μM. This binding affinity is 10,000-fold greater than the RNA molecule's affinity for caffeine, which differs from theophylline only by a methyl group at nitrogen atom N-7. Analysis by nuclear magnetic resonance indicates that this RNA molecule undergoes a significant change in its conformation or dynamics upon theophylline binding. Binding studies of compounds chemically related to theophylline have revealed structural features required for the observed binding specificity. These results demonstrate the ability of RNA molecules to exhibit an extremely high degree of ligand recognition and discrimination.