In vitro sulfadoxine and pyrimethamine resistance has been associated with point mutations in the dihydropteroate synthase and dihydrofolate reductase domains, respectively, but the in vivo relevance of these point mutations has not been well established. To analyze the correlation between genotype and phenotype, 10 Cameroonian adult patients were treated with sulfadoxine-pyrimethamine and foll...

A new fluorescent methotrexate analogue (PT430) was synthesized as a reported ligand for dihydrofolate reductase. The analogue was prepared by attachment of lysine in place of the glutamate side chain of methotrexate and conjugation to fluorescein isothiocyanate via the epsilon-amino group of lysine. Spectrophotometric enzyme inhibition assays showed PT430 to be about one-tenth as potent as met...

1. Nano R, Invernizzi R, Rezzani R, Gerzeli G. Qualitative and quantitative study of dihydrofolate reductase in myelodysplastic syndromes. Acta Haematol 1988; 79: 198-201. 2. Nano R, Gerzeli G, Invernizzi R, Supino R. A qualitative and quantitative cytochemical assay of dihydrofolate reductase in erythroid cells. Acta Histochem 1989; 85:51-8. 3. Greenberg P, Cox C, Le Beau MM, et al. Internatio...

VIDENCE for the occurrence of mutation in the dihydrofolate reductase E gene of Diplococcus pneumoniae, which alters both the amount and structure of the corresponding enzyme, has been presented in two previous reports from this laboratory. (SIROTNAK and HACHTEL 1969; SIROTNAK, WILLIAMS and HACHTEL 1969). This form of dual biochemical effect is similar in some respects to that observed in the L...

1 The binding of a series of amide derivatives of methotrexate to Lactobacillus casei dihydrofolate reductase has been studied by inhibition constant measurements and by 'H n.m.r. spectroscopy. 2 Amide modification of the a-carboxylate of methotrexate was found to prevent interaction of the y-carboxylate with the imidazole of His 28. 3 Estimates of the contributions to the binding energy from t...

The biosynthesis of tetrahydrobiopterin from either dihydroneopterin triphosphate, sepiapterin, dihydrosepiapterin or dihydrobiopterin was investigated using extracts from human liver, dihydrofolate reductase and purified sepiapterin reductase from human liver and rat erythrocytes. The incorporation of hydrogen in tetrahydrobiopterin was studied in either 2H2O or in H2O using unlabeled NAD(P)H ...

From a single amethopterin-resistant organism, Streptococcus faecium var. durans strain A, two different dihydrofolate reductases have been obtained as essentially homogeneous proteins in good yield. One of the reductases has a similar substrate specificity and turnover number (about 8000 moles per min per mole of enzyme) to the single reductase found in the amethopterin-sensitive strain of S. ...

From a single amethopterin-resistant organism, Streptococcus faecium var. durans strain A, two different dihydrofolate reductases have been obtained as essentially homogeneous proteins in good yield. One of the reductases has a similar substrate specificity and turnover number (about 8000 moles per min per mole of enzyme) to the single reductase found in the amethopterin-sensitive strain of S. ...