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Science 11 March 1994:
Vol. 263. no. 5152, pp. 1425 - 1429
DOI: 10.1126/science.7510417
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Articles

Science, Vol 263, Issue 5152, 1425-1429
Copyright © 1994 by American Association for the Advancement of Science

articles

High-resolution molecular discrimination by RNA

RD Jenison, SC Gill, A Pardi, and B Polisky

NeXagen, Inc., Boulder, CO 80301.

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 Kd of 0.1 microM. 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.


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