Mehta J R, Przybylski M, Ludlum D B
Cancer Res. 1980 Nov;40(11):4183-6.
Phosphoramide mustard, an active metabolite of cyclophosphamide, has been reacted separately with guanosine and deoxyguanosine in aqueous solution at pH 7.4. The major adduct which was formed in each case has been isolated by reverse-phase high-pressure liquid chromatography. The structure of the major adduct, as determined by a combination of ultraviolet and field desorption mass spectrometry, is that of phosphoramide mustard, one arm of which has reacted with guanosine or deoxyguanosine in position 7. These adducts are much less stable than was 7-methylguanosine, and they decompose with a half-life of 1.3 hr at 37 degrees and pH 7.4. This instability may contribute to the action of phosphoramide mustard at a molecular level.
磷酰胺氮芥是环磷酰胺的一种活性代谢产物,已在pH 7.4的水溶液中分别与鸟苷和脱氧鸟苷发生反应。每种情况下形成的主要加合物已通过反相高压液相色谱法分离出来。通过紫外和场解吸质谱联用确定的主要加合物的结构是磷酰胺氮芥的结构,其一条臂已与鸟苷或脱氧鸟苷的7位发生反应。这些加合物的稳定性远低于7-甲基鸟苷,在37℃和pH 7.4条件下,它们的半衰期为1.3小时,会发生分解。这种不稳定性可能在分子水平上有助于磷酰胺氮芥发挥作用。