Characterization of melphalan-glutathione adducts whose formation is catalyzed by glutathione transferases.
Characterization of melphalan-glutathione adducts whose formation is catalyzed by glutathione transferases.
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谷胱甘肽转移酶催化形成的美法仑-谷胱甘肽加合物的表征。
DOI：
10.1016/0006-2952(86)90444-2
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发表时间：
1986
影响因子：
5.8
通讯作者：
Hilton,J
中科院分区：
文献类型：
--
作者：
Dulik,DM;Fenselau,C;Hilton,J
许多作者描述了巯基水平升高与烷化剂耐药性之间的关联。目前对抗肿瘤氮芥（例如美鲁哈兰）产生耐药性的解释。包括药物摄入受损的证据 111 和细胞内谷胱甘肽 I2-41 水平升高：最近，Vistica 及其同事 [S] 报道，对马法兰具有抗性的小鼠 L1210 细胞中还原型谷胱甘肽和谷胱甘肽-S-转移酶的水平均升高。然而，这些研究都没有表明马法兰-谷胱甘肽加合物的直接形成是这种现象中潜在的重要考虑因素。本研究的目的是表征美法仑 (1) 和谷胱甘肽之间的结合产物，其形成由胞质和微粒体谷胱甘肽-S-转移酶催化。反应产物已被鉴定为通过置换芥子部分中的两个氯基团形成的二谷胱甘肽缀合物，以及通过置换一个氯基团形成的单谷胱甘肽缀合物。
A number of authors have described an association between elevated sulfhydryl levels and resistance to alkylating agents. Current explanations for the development of resistance to antineoplastic nitrogen mustards, such as meluhalan. include evidence of impaired drug intake 111 and increased levels of intracellular glutathione I2-41: Recently, Vistica and coworkers [S] reported that murine L1210 cells resistant to melphalan contain elevated levels of both reduced glutathione and glutathione-S-transferase. However, none of these studies has suggested the direct formation of a melphalan-glutathione adduct as being a potentially important consideration in this phenomenon. The objective of this study was to characterize the conjugation products between melphalan (1) and glutathione whose formation is catalyzed by both cytosolic and microsomal glutathione-S-transferases. The reaction products have been identified as the diglutathione conjugate formed by displacing both chloride groups in the mustard moiety, and a monoglutathione conjugate formed by displacing one chloride group.