Folate Biochemistry in Relation to Antifolate Selectivity

摘要: This review will deal with advances in folate biochemistry related to antifolate toxicity and selectivity. Because of the interrelatedness reactions metabolism, alterations activity any enzyme, cellular transport system, as well concentration metabolite may be relevant cytotoxicity Therefore, it is difficult predict results inhibiting a given enzyme on For example, many experimental systems, cytotox-icity methotrexate caused by its ability inhibit dihydrofolate reductase, resulting lowered thymidylate formation, leading lethal defects DNA. However, selec-tiviry often dependent differential uptake polyglutamylation. Favorable clinical aminopterin, forerunner methotrexate, acute leukemia children were reported Farber et al. (1) 1948. work depended knowledge generated at American Cyanamid Company, Pearl River, NY, structure folic acid chemical synthesis analogs addition insightful observations group (1). was done before role tetrahydrofolates metabolism single carbon units known. The present discussion current literature folates offered hope that, powerful analytical, structural, molecular genetic, synthetic methods now available, new approaches selective can generated.