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throughput screening strategies and the development of structure activity relationships for compound leads. In addition to
traditional methods, such as filter binding, gel mobility shift assay and various fluorescence techniques, newer methods such
as surface plasmon resonance and mass spectrometry are being used for the study of RNA protein interactions.
NA, unlike DNA, folds into a myriad of tertiary molecules, thus making RNA an interesting target for
structures that are responsible for its diverse func- therapeutic intervention. The interaction of a natural
Rtions in cells. In addition to its role as a mediator compound or a chemically designed drug with an
of genetic information from DNA to protein, RNA RNA molecule might influence the biological activity
serves as genetic material (in some viruses), as a struc- of the RNA by preventing or enhancing the binding
tural component of many ribonucleoprotein (RNP) of effector proteins, by inhibiting RNA catalysis or by
particles and in some cases as a catalytic subunit of forcing an alternative conformation on the RNA7,8.
RNPs1. In most instances, RNA is associated with The ability of small molecules to interact with RNA
RNA-binding proteins (RBPs) that protect, stabilize, has been recognized for some time. Antibiotics are an
package or transport RNA, mediate RNA interactions example of a class of naturally occurring compounds
with other biomolecules or act catalytically on RNA2,3. that interact with RNA. Many antibiotics are known
The structural information obtained for RNA alone4,5 to target the ribosomal RNA (rRNA) of prokaryotes,
and RNA protein complexes3 has elucidated a variety thus affecting translation9,10. These antibiotics are
of RNA tertiary structures and diverse modes for chemically and structurally diverse, several examples of
RNA protein interaction6. The specific interaction of which are shown in Fig. 1. The site and mechanism of
proteins with highly structured RNAs should make action of some of these antibiotics are summarized in
it possible to target unique RNA motifs with small Table 1. Aminoglycoside antibiotics, the most well-
characterized RNA-binding antibiotics, target the 16S
rRNA near the A-site in the 30S ribosomal subunit
K.A. Xavier (xavier@messagepharm.com), P.S. Eder and T. Giordano
(decoding of the mRNA takes place at the A-site,
are at Message Pharmaceuticals, 30 Spring Mill Drive, Malvern, PA
19355, USA. where the anticodon of a tRNA forms base pairs with
TIBTECH AUGUST 2000 (Vol. 18) 0167-7799/00/$ see front matter © 2000 Elsevier Science Ltd. All rights reserved. PII: S0167-7799(00)01464-5 349
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