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), MTXαPhenylalanine and arginine derivatives were synthesized by solid phase peptide synthesis. The product was purified by HPLC to obtain single peak of HPLC. Its molecular weight was in accordance with the theoretical value by mass spectrometry. MTX  α  phenylalanine carboxypeptidase  A treatment, can be completely degraded to MTX. In vitro cytotoxicity test, the difference between the two activities in more than 100 times, suggesting MTX  α  phenylalanine is an ideal prodrug.