Interaction of the aziridine moiety of RSU-1069 with nucleotides and inorganic phosphate. Implications for alkylation of DNA.
The aziridine moiety of RSU-1069 (1-(2-nitro-1-imidazolyl)-3-(1-aziridino-2-propanol] alkylates inorganic phosphate and a range of nucleotides in aqueous solutions of pH 7.0. From the rate constants obtained and a study of the adducts formed it is demonstrated that phosphate is a major target on nucleotides at neutral pH, although additional sites may exist particularly on dGMP and dAMP. From the dependence of reactivity on pH and the influence of ionic strength, it is established that the protonated aziridine is the reactive species and that hydrolysis is insignificant when compared to the rate of phosphorylation. The reaction kinetics detailed in this study are discussed in terms of DNA alkylation and strand breakage effected by the aziridine moiety of RSU-1069.
D000218:Adamantane / Q000031:analogs & derivatives / Q000378:metabolism; D000478:Alkylation; D000818:Animals; D002853:Chromatography, Liquid; D004247:DNA / Q000378:metabolism*; D003848:Deoxyguanine Nucleotides / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008433:Mathematics; D008920:Misonidazole / Q000031:analogs & derivatives* / Q000378:metabolism; D009711:Nucleotides / Q000378:metabolism*; D009994:Osmolar Concentration; D010710:Phosphates / Q000378:metabolism*
D003848:Deoxyguanine Nucleotides; D009711:Nucleotides; D010710:Phosphates; C016358:2,4-diamino-5-adamantyl-6-methylpyrimidine; C007257:2'-deoxyguanosine 5'-phosphate; C041712:1-(2-nitro-1-imidazolyl)-3-aziridino-2-propanol; D008920:Misonidazole; D004247:DNA; D000218:Adamantane