Fraenkel-Conrat H, Singer B
Department of Molecular Biology, Lawrence Berkeley Laboratory, University of California, Berkeley 94720.
Proc Natl Acad Sci U S A. 1988 Jun;85(11):3758-61. doi: 10.1073/pnas.85.11.3758.
The exocyclic amino groups of ribonucleosides and deoxyribonucleosides react rapidly at ambient temperature with acetaldehyde and alcohols to yield mixed acetals [--NH--CH(CH3)OR]. Nucleotides and nucleoside di- and triphosphates also react. Depending on the nucleoside used and on the relative amounts of aldehyde, alcohol, and water, preparative reactions reach equilibrium with yields up to 75% in a few hours. The structures have been confirmed by fast atom bombardment MS and proton NMR. Half-lives at 37 degrees C have been determined, and maximum stability is in the pH range of 7.5-9.5. In the absence of alcohol, acetaldehyde-nucleoside adducts could be isolated at 4 degrees C, but these were too unstable to characterize except for their UV spectra, also at 4 degrees C. Ethanol is often present in human blood and tissues, and acetaldehyde is its initial metabolic product, as well as being formed by many other metabolic processes. Both chemicals have separately been implicated in carcinogenic and other cytopathologic processes, but no cooperative mechanism has been proposed. The reactions reported here are of biological concern because they also occur in dilute aqueous solution. These findings supply a mechanism by which ethanol can be covalently bound to nucleic acids under physiological conditions.
核糖核苷和脱氧核糖核苷的环外氨基在室温下能迅速与乙醛和醇类反应，生成混合缩醛[--NH--CH(CH3)OR]。核苷酸以及核苷二磷酸和三磷酸也会发生反应。根据所用核苷以及醛、醇和水的相对量，制备反应在数小时内达到平衡，产率高达75%。其结构已通过快速原子轰击质谱和质子核磁共振得到证实。已测定了37摄氏度时的半衰期，最大稳定性处于7.5 - 9.5的pH范围内。在没有醇的情况下，乙醛 - 核苷加合物可在4摄氏度下分离出来，但除了在4摄氏度下的紫外光谱外，这些加合物过于不稳定，无法进行表征。乙醇常存在于人体血液和组织中，乙醛是其初始代谢产物，也是许多其他代谢过程形成的产物。这两种化学物质都分别与致癌和其他细胞病理过程有关，但尚未提出协同作用机制。此处报道的反应具有生物学意义，因为它们也发生在稀水溶液中。这些发现提供了一种机制，通过该机制乙醇在生理条件下可与核酸共价结合。
