ORGANIC
LETTERS
2006
Vol. 8, No. 17
3753-3756
C6-Substituted Analogues of
8-Azanebularine: Probes of an
RNA-Editing Enzyme Active Site
Olena Maydanovych and Peter A. Beal*
Department of Chemistry, UniVersity of Utah, Salt Lake City, Utah 84112
Received June 2, 2006
ABSTRACT
We describe the synthesis of derivatives of 8-azanebularine, a known inhibitor of adenosine deaminases including the RNA-editing enzyme
ADAR2. 6-Methyl, 6-hydroxymethyl, 6-cyano, and 6-mercapto derivatives were obtained from 6-bromo precursors using different cross-coupling
or substitution reactions. The C6-methyl derivative was incorporated into an RNA substrate for ADAR2 via the phosphoramidite. Quantitative
gel mobility shift experiments with the resulting RNA indicate that methylation at C6 dramatically reduces the affinity of 8-azanebularine for
ADAR2.
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10.1021/ol061354j CCC: $33.50
© 2006 American Chemical Society
Published on Web 07/21/2006