Niedernhofer L J, Riley M, Schnetz-Boutaud N, Sanduwaran G, Chaudhary A K, Reddy G R, Marnett L J
Department of Biochemistry, Center in Molecular Toxicology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-0146, USA.
Chem Res Toxicol. 1997 May;10(5):556-61. doi: 10.1021/tx960191c.
The stability of the major adduct formed between the endogenous product malondialdehyde (MDA) and deoxyguanosine, a pyrimidopurinone termed M1G-dR, was tested under a variety of conditions required for nucleic acid manipulation. M1G-dR was found to be stable at neutral pH and 37 degrees C but to be unstable when stored at -20 degrees C in the presence of Tris buffers. A new product with a characteristic absorption band at 350 nm was identified by 1H-NMR as an enamino-imine comprised of one molecule of Tris, one molecule of MDA, and deoxyguanosine. The formation of the conjugate was observed on reaction of Tris with M1G-dR or its ring-opened derivative N2-(3-oxo-1-propenyl)deoxyguanosine. The Tris-M1G-dR conjugate was unstable in aqueous solutions at room temperature, undergoing hydrolysis. However, the Tris conjugate of M1G base remained stable at room temperature in organic solvent. The isolation and properties of a conjugate between M1G-dR and Tris suggest that cross-links may form by reaction of MDA with DNA but they are likely to be unstable to hydrolysis.
对内源性产物丙二醛（MDA）与脱氧鸟苷形成的主要加合物（一种称为M1G-dR的嘧啶嘌呤酮）在核酸操作所需的各种条件下的稳定性进行了测试。发现M1G-dR在中性pH和37℃下稳定，但在Tris缓冲液存在下于-20℃储存时不稳定。通过1H-NMR鉴定出一种在350nm处具有特征吸收带的新产物，它是由一分子Tris、一分子MDA和脱氧鸟苷组成的烯胺亚胺。在Tris与M1G-dR或其开环衍生物N2-(3-氧代-1-丙烯基)脱氧鸟苷反应时观察到共轭物的形成。Tris-M1G-dR共轭物在室温下的水溶液中不稳定，会发生水解。然而，M1G碱基的Tris共轭物在室温下于有机溶剂中保持稳定。M1G-dR与Tris之间共轭物的分离和性质表明，MDA与DNA反应可能形成交联，但它们可能对水解不稳定。
