Basu A K, O'Hara S M, Valladier P, Stone K, Mols O, Marnett L J
Department of Chemistry, Wayne State University, Detroit, Michigan 48202.
Chem Res Toxicol. 1988 Jan-Feb;1(1):53-9. doi: 10.1021/tx00001a010.
Malondialdehyde and a series of acrolein derivatives substituted in the beta-position with good leaving groups react with guanine and guanine nucleosides to form two different types of adducts. The reaction with guanosine is typical. One adduct exhibits ultraviolet absorbance maxima at 253, 319, and 348 nm and is fluorescent. Its NMR spectrum exhibits three new aromatic proton resonances derived from malondialdehyde. The mass spectrum exhibits an M + 1 at 320. The spectroscopic properties are consistent with the structure, 3-beta-D-erythro-pentofuranosyl-pyrimido[1,2-alpha]purin-10(3H)-one (PyP-ribose). The second guanosine adduct is an equal mixture of diastereomers that exhibit ultraviolet maxima at 217 and 244 nm and mirror image circular dichroism spectra. The NMR spectrum and mass spectrum (M + 1 = 392) indicate the addition of two molecules of MDA to one molecule of guanosine. Two-dimensional NMR (COSY) analysis reveals the presence of propano and enal functionalities. The spectroscopic and chemical properties suggest an oxadiazabicyclo[3.3.1]nonene structure that is confirmed by X-ray crystallography. Comparison of the deoxyguanosine adducts of malondialdehyde to those of the structurally related carbonyl compounds, methyl glyoxal and acrolein, provides a structural basis to explain the unique ability of malondialdehyde to induce frameshift mutations in bacterial mutagenesis systems.
丙二醛以及一系列在β位被良好离去基团取代的丙烯醛衍生物与鸟嘌呤和鸟嘌呤核苷反应，形成两种不同类型的加合物。与鸟苷的反应具有代表性。一种加合物在253、319和348 nm处有紫外吸收最大值且具有荧光性。其核磁共振谱显示出源自丙二醛的三个新的芳香质子共振峰。质谱显示其分子量加1为320。光谱性质与结构3-β-D-赤藓糖基-嘧啶并[1,2-α]嘌呤-10(3H)-酮（PyP-核糖）一致。第二种鸟苷加合物是一对非对映异构体的等量混合物，在217和244 nm处有紫外最大值，且具有镜像圆二色光谱。核磁共振谱和质谱（分子量加1 = 392）表明一分子鸟苷与两分子丙二醛加成。二维核磁共振（COSY）分析揭示了丙醇和烯醛官能团的存在。光谱和化学性质表明其为恶二氮杂双环[3.3.1]壬烯结构，这一点通过X射线晶体学得以证实。将丙二醛与结构相关的羰基化合物甲基乙二醛和丙烯醛的脱氧鸟苷加合物进行比较，为解释丙二醛在细菌诱变系统中诱导移码突变的独特能力提供了结构基础。
