Robert Ferone

Multisubstrate Analogue Inhibitors of Glycinamide Ribonucleotide Transformylase Based on 5-Deazaacyclo Tetrahudrofolate (5-DACTHF)

N 10 -Substituted acetyl derivatives of 5-DACTHF are less active in general than the parent. However, multisubstrate analogue inhibitors that are 1000-fold more potent were synthesized, and N 10 -pyruvoyl-5-DACTHF serves as a precursor for a metabolically assembled multisubstrate analogue

Inhibition of dihydrofolate synthetase by folate, homofolate, pteroate and homopteroate and their reduced forms

Dihydrofolate (H2-folate) synthetase (EC 6.3.2.12) was isolated from Escherichia coli B. A radiochemical assay was developed to determine the activity of H2-folate synthetase in order to study the effects of folate metabolites and antimetabolites which would interfere with the microbiological assay method previously used. The effects of folate and pteroate derivatives on the activity of this enzyme were investigated to determine if inhibition of this enzyme could constitute a site of action for these compounds as chemotherapeutic agents or a site of metabolic regulation. H2-folate synthetase was inhibited by its product, H2-folate, and by the antimetabolite dihydrohomopteroate, with apparent Ki values of 23.4 and 9.2 muM, respectively.