Stereospecificity at carbon 6 of fomyltetrahydrofolate as a competitive inhibitor of transport and cytotoxicity of methotrexate in vitro.
Stereospecificity at carbon 6 of fomyltetrahydrofolate as a competitive inhibitor of transport and cytotoxicity of methotrexate in vitro.
复制标题
甲酰四氢叶酸在碳 6 上的立体特异性作为体外甲氨蝶呤运输和细胞毒性的竞争性抑制剂。
DOI：
10.1016/0006-2952(79)90599-9
复制
发表时间：
1979
影响因子：
5.8
通讯作者：
J. Montgomery
中科院分区：
文献类型：
--
作者：
F. Sirotnak;P. L. Chello;D. M. Moccio;R. Kisliuk;G. Combépine;Y. Gaumont;J. Montgomery
在L1210、S180和Ehrlich细胞中，非天然的非对映异构体l-5-甲酰基四氢叶酸在载体介导的膜转运过程中，作为竞争抑制[~3H]氨甲喋呤内流的作用比天然的非对映异构体低20倍。KI，天然衍生物为1.84~2.29μM，非天然衍生物为35.2~53.8μM。化学合成的混合物含有等量的天然和非天然非对映异构体，其KI值比天然非对映异构体的值大2倍。非天然的非对映异构体的效果比天然的非对映异构体低100倍，化学合成的混合物在防止甲氨蝶呤抑制培养的L1210细胞生长方面的效果比天然的非对映异构体低2倍。这些结果表明，非天然的非对映异构体与天然的非对映异构体或甲氨蝶呤在这些小鼠肿瘤细胞中的运输竞争相对无效。
The unnatural diastereoisomer ofl-5-formyltetrahydrofolate was 20-fold less effective as a competitive inhibitor of [3H] methotrexate influx than the natural diastereoisomer during carrier-mediated membrane transport in L1210, S180 and Ehrlich cells. Values derived forKi, were 1.84 to 2.29 μM for the natural derivative and 35.2 to 53.8 μM for the unnatural derivative. Values forKiderived with a chemically synthesized mixture containing equal amounts of both natural and unnatural diastereoisomers were 2-fold greater than values obtained for the natural diastereoisomer. The unnatural diastereoisomer was 100-fold less effective and the chemically synthesized mixture was 2-fold less effective than the natural diastereoisomer in preventing inhibition by methotrexate of L1210 cell growth in culture. These results indicate that the unnatural diastereoisomer competes relatively ineffectively with the natural diastereoisomer or methotrexate for transport in these murine tumor cells.