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The role of folylpolyglutamates in biosynthetic processes has gained increasing importance with the recognition that these com pounds are not only the forms of folate co-factors that accumulate within cells, but, in addition, are the preferred substrates for folate dependent reactions in eukaryotic cells. More recently attention has turned to the potential importance of the polyglutamyl derivatives of methotrexate that have been detected in normal and malignant cells both in vitro and in vivo. The biochemical trans formation of this important chemotherapeutic agent is of particular significance since polyglutamyl derivatives of methotrexate are not only potent inhibitors of the target enzyme...