Andrievsky G V, Sukhodub L F, Pyatigorskaya T L, Boryak O A, Shelkovsky V S
Kharkov Research Institute for Therapy, UkrSSR Ministry of Health, Kharkov.
Biol Mass Spectrom. 1991 Nov;20(11):665-8. doi: 10.1002/bms.1200201103.
By the methods of fast atom bombardment (FAB) mass spectrometry, thin-layer chromatography and ultraviolet absorption spectroscopy adducts have been studied which are formed by an antitumour alkylating drug thiotepa both in a model system, containing only deoxyguanosine (dGuo), and in DNA. Analysis of the model reaction mixture (dGuo + thiotepa) by FAB mass spectrometry permitted observation of adducts dGuo thiotepa, 2dGuo thiotepa, and also the products of their further modification in solution, which occurs by hydrolysis of the glycosidic bond and also by opening of the imidazole ring. In the case of DNA FAB mass spectrometry made it possible to characterize adducts of thiotepa with guanosine (Gua) and adenosine (Ade) without their preliminary purification. The site of alkylation of Gua in both dGuo and DNA is N7, and that of Ade in DNA is N3. The application of the results to the study of the molecular mechanism of the antitumour action of thiotepa is discussed.
通过快速原子轰击（FAB）质谱法、薄层色谱法和紫外吸收光谱法，研究了抗肿瘤烷基化药物噻替哌在仅含脱氧鸟苷（dGuo）的模型体系以及在DNA中形成的加合物。通过FAB质谱法对模型反应混合物（dGuo + 噻替哌）进行分析，可观察到加合物dGuo噻替哌、2dGuo噻替哌，以及它们在溶液中进一步修饰的产物，这些产物是通过糖苷键水解以及咪唑环开环产生的。对于DNA，FAB质谱法能够在不进行初步纯化的情况下对噻替哌与鸟苷（Gua）和腺苷（Ade）的加合物进行表征。在dGuo和DNA中，Gua的烷基化位点均为N7，而在DNA中Ade的烷基化位点为N3。文中还讨论了这些结果在研究噻替哌抗肿瘤作用分子机制方面的应用。
