The search for effective therapeutics for cryptosporidiosis and toxoplasmosis has led to the discovery of novel inhibitors of dihydrofolate reductase (DHFR) that possess high ligand efficiency: compounds with high potency and low molecular weight. Detailed analysis of the crystal structure of dihydrofolate reductase-thymidylate synthase from Cryptosporidium hominis and a homology model of DHFR ...

This paper is based on the neural folding architecture (FA). The FA is a recurrent neural network architecture which is especially suited for adaptive structure processing, i.e. learning approximations of mappings from symbolic term structures to IR n. The main objective of this paper is to demonstrate that the FA can be successfully applied to approximate quantitative structure activity relati...

Thymidylate synthetase and dihydrofolate reductase exist as a bifunctional protein in a number of species of protozoa which span diverse groups of the subkingdom. The enzymes copurify upon gel filtration and on affinity chromatography columns specific for dihydrofolate reductase. The bifunctional protein has been found in species of Crithidia, Leishmania, Trypanosoma, Plasmodium, Eimeria, Tetra...

using mutation specific pcr assay and analysis of position 108 amino acid in dihydrofolate reductase-thymidilate synthase gene in 70 plasmodium falciparum isolates of malarial patients from southern areas of iran, showed 4 different situations: iwild type (108-ser) ii-mutant type (108-thr) iii-mutant type (108-asn) and iv-mixed wild and mutant type (108-ser+thr) with frequency of 58(82.8%), 2(2...

Monospecific (affinity-purified) anti-(yeast glucose-6-phosphate dehydrogenase) IgG inhibits three different NADPH-requiring enzymes, chicken liver dihydrofolate reductase, pigeon liver fatty acid synthetase and chicken liver malic enzyme. The inhibition of all three enzymes was approx. 50% in a 2h incubation with 100 micrograms of IgG. Similarly, with several different NADH-requiring enzymes, ...

Inhibitors of folic acid synthesis were compared alone and in different combinations in the therapy of pneumocystosis in immunosuppressed rats. Sulfonamides (sulfamethoxazole, sulfadiazine, and sulfadoxine) and sulfones (dapsone) used alone were very active against Pneumocystis carinii, as judged by histologic examination of the lungs and by organism quantitation. Improved efficacy could not be...

Pistacia integerrima Stew ex Brandis is a valued medicinal plant used for curing various diseases such as diarrhea, fever, liver disorder, pain, asthma, and inflammation. The aim of this study was the isolation bioactive leishmanicidal agents from methanolic extract. extract led to flavonoids 3,5,7,4/-tetrahydroxy-flavanone (1). isolated compound 1 were tested antileishmanial effect. showed per...

We introduce a novel approach for structure activity relationship analysis based on the use of a special kernel. The kernel eÆciently performs Gram-Schmidt orthogonalisation in a kernel de ned feature space. We show that support vector machines in conjunction with Gram-Schmidt kernel, a recent method to extract features, can be adopted successfully to predict the inhibition of dihydrofolate red...

With vital yeast cells, a hybrid protein consisting of the amino-terminal third of the precursor to cytochrome b2 and of the entire dihydrofolate reductase was arrested on the import pathway into mitochondria. Accumulation of the protein in the mitochondrial membranes was achieved by inducing a stable tertiary structure of the dihydrofolate reductase domain. Thereby, three salient features of m...

Sequences that are capable of restoring mitochondrial targeting to a truncated yeast cytochrome c oxidase subunit IV presequence are encoded within the genome of Escherichia coli and within the gene for a higher eukaryotic cytosolic protein, mouse dihydrofolate reductase. These sequences, which resemble authentic presequences in their overall amino acid composition and degree of hydrophobicity,...