title: C6-substituted analogues of 8-azanebularine: probes of an RNA-editing enzyme active site.
abstract: [reaction: see text] 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.
authors.affiliation: Department of Chemistry, University of Utah, Salt Lake City, Utah 84112, USA.
authors.forename: Olena
authors.initials: O
authors.lastname: Maydanovych
authors.forename: Peter A
authors.initials: PA
authors.lastname: Beal
mesh_terms: D000243:Adenosine Deaminase; D058892:Adenosine Deaminase Inhibitors; D001665:Binding Sites; D015394:Molecular Structure; D010165:Palladium / Q000737:chemistry; D011684:Purine Nucleosides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D012313:RNA / Q000737:chemistry* / Q000378:metabolism; D017393:RNA Editing / Q000187:drug effects; D016601:RNA-Binding Proteins; D012263:Ribonucleosides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013329:Structure-Activity Relationship
chemical_list: C520167:8-azanebularine; D058892:Adenosine Deaminase Inhibitors; D011684:Purine Nucleosides; D016601:RNA-Binding Proteins; D012263:Ribonucleosides; D010165:Palladium; D012313:RNA; C567955:ADARB1 protein, human; D000243:Adenosine Deaminase