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.
ASJC Scopus subject areas
- Molecular Medicine