Synthesis and enantioselective mutagenicity of azidoalanine in Salmonella typhimurium.
Azide mutagenicity involves the requisite formation of the putative novel aminoacid metabolite, beta-azidoalanine. The role of this metabolite, however, is unclear. In order to confirm the identity of this metabolite and provide additional information on possible stereochemical requirements for mutagenicity, authentic racemic and L-azidoalanine were synthesized by an unambiguous route and tested for mutagenicity in Salmonella typhimurium TA100, TA1535, hisG46 and Escherichia coli WP2-. A marked antipodal potency ratio was observed in strains TA100 and TA1535 when racemic and L-azidoalanine were compared. The mutagenic activity resided primarily in the L-isomer. The molar potency of L-azidoalanine in TA100 and TA1535 was nearly identical to that of azide. The lack of mutagenic response for racemic or L-azidoalanine in hisG46 and E. coli WP2- was like that reported for azide and is consistent with similar modes of action for these agents.
D000409:Alanine / Q000031:analogs & derivatives* / Q000633:toxicity; D001386:Azides / Q000633:toxicity*; D004926:Escherichia coli / Q000187:drug effects; D009152:Mutagenicity Tests; D012486:Salmonella typhimurium / Q000187:drug effects*; D013237:Stereoisomerism
D001386:Azides; C039309:azidoalanine; D000409:Alanine