氨甲喋呤-α-肽的固相合成

THE SOLID PHASE SYNTHESIS OF METHOTREXATE α PEPTIDES

用固相肽合成法合成了氨甲喋呤（ＭＴＸ）与ＭＴＸα苯丙氨酸及精氨酸衍生物，产物不经进一步分离纯化即可达到ＨＰＬＣ单峰，质谱分析其分子量符合理论值。ＭＴＸα苯丙氨酸经羧肽酶Ａ处理后，可完全降解为ＭＴＸ。体外细胞毒性试验，两者活性差异在１００倍以上，提示ＭＴＸα苯丙氨酸是一理想的前体药物。

Methotrexate(MTX) and the methotrexate α peptides(MTX α phenylalanine and MTX α arginine ie. MTX α Phe and MTX α Arg) were prepared with the technique of solid phase peptide synthesis. Its purity was verified as a single peak by HPLC and its molecular weight was measured by mass spectrometry. MTX α Phe could be hydrolyzed to MTX by carboxypeptidase A. The cytotoxic effect of released MTX was found to be 100 times stronger than that of the peptide in vitro . It is suggested that MTX α Phe is a satisfactory prodrug in the treatment of cancer.