Mofebutazon, in contrast to phenylbutazon, inhibits dihydrofolate reductase in a concentration-dependent manner. An apparent Ki for mofebutazon and dihydrofolate reductase in the presence of NADPH as electron donor and dihydrofolate as electron acceptor of approximately 0.2 mM was calculated.

A strain of Escherichia coli with the fol gene deleted and a kan gene inserted in its place was created for use in cloning and isolation of mutant dihydrofolate reductase. Southern blot analysis and dihydrofolate reductase enzyme assays confirmed the delta fol::kan genotype. A thyA mutation accompanied the fol deletion and is required for survival of a dihydrofolate reductase-deficient strain.

Chromosomal aberrations and dihydrofolate reductase gene amplification are observed in L5178Y mouse lymphoma cells after treatment with hydroxyurea. The types of aberrations include polyploidy, endoreduplication, chromosome fragmentation, and the presence of extrachromosomal DNA. Hydroxyurea-treated cells analyzed by cell sorting showed a subpopulation of cells with increased DNA and increased ...

background: protozoa related to trypanosome family including leishmania , synthesize enzymes to escape from drug therapy. one of them is ptr1 that its enzymatic activity is similar to dihydrofolate reductase (dhfr). dihydrofolate reductase - thymidylate synthase has a major role in dna synthesis, if it is inhibited, the result would be the death of parasite. since ptr1 activity is similar to dh...

background: the recently reported resistance to antimalarials contributes to making the control of ma­laria more difficult. there is a need to evaluate the current antimalaria regimens to prevent this emerging problem. the aim of this study was to determine dihydrofolate reductase-thymidylate synthase gene mu­tation ( pvdhfr ) regarding antifulate resistance in plasmodium vivax . methods : from...

Deoxyribonucleic acid fragments containing the structural genes for several trimethoprim-resistant dihydrofolate reductases from naturally occurring plasmids were inserted into small cloning vehicles. The genetic expression of these hybrid plasmids was studied in purified Escherichia coli minicells. The type I dihydrofolate reductase, encoded by plasmid R483 and residing within transposon 7 (Tn...

Quantitative S1 nuclease mapping studies were performed with uniformly labeled RNA probes, containing contiguous dihydrofolate reductase exon and intron sequences, and total RNA isolated from KB7B cells exposed to 5-fluorouracil for 5 days. Dihydrofolate reductase RNA containing both exon 1 and intron I, or exon 5 and a portion of intron V, increased up to 5-fold in cells grown in the presence ...

background: trastuzumab (herceptin) is a humanized monoclonal antibody (mab) which is used for specific treatment of metastatic breast cancer in patients with overexpression of her2/neu receptor. in this study, we have attempted to develop a biosimilar version of trastuzumab mab. methods: according to in silico studies, the heavy and light chains of trastuzumab mab were designed and constructed...

A retrospective study of clinical resistance to methotrexate (MTX) was performed on 29 archival specimens of frozen lymphoblasts obtained from children with acute lymphoblastic leukemia (ALL), including 19 at initial presentation and 10 at first relapse. Blasts were assayed for dihydrofolate reductase and MTX transport by flow cytometry using the fluorescent methotrexate analog, PT430 (Rosowsky...

Refined crystal structures are reported for complexes of Escherichia coli and chicken dihydrofolate reductase containing the antibiotic trimethoprim (TMP). Structural comparison of these two complexes reveals major geometrical differences in TMP binding that may be important in understanding the stereo-chemical basis of this inhibitor's selectivity for bacterial dihydrofolate reductases. For TM...