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analysis
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selectable and amplifiable gene marker for e.g. somatic cell hybridization studies
analysis
development of a survival protein-fragment complementation assay based on dihydrofolate reductase. Proteins of interest are fused to complementary fragments of dihydrofolate reductase. If the proteins of interst interact physically, the dihydrofolate complementary fragments are brought together and fold into the native structure, reconstituting its activity
analysis
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development of a yeast protein fragment complementation assay system using dihydrofolate reductase and application for investigating eukaryotic protein-protein interaction in vivo. Fusion of human oncoprotein Ras and Ras-binding domain of Raf-1 to dihydrofolate reductase as a model and evaluation of interaction between these proteins
analysis
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heteroduplex tracking assay to detect dihydrofolate redctase L164-mutations in variants representing 1% of the parasites in an individual host
analysis
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use of multiple protein structure technique for structure-based drug discovery. Construction of receptor-based pharmacophores using multiple X-ray crystallographic structures. Models incorporate a fair degree of protein flexibility and are highly selective for known inhibitors over drug-like non-inhibitors
analysis
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use of multiple protein structure technique for structure-based drug discovery. Construction of receptor-based pharmacophores using multiple X-ray crystallographic structures. Models incorporate a fair degree of protein flexibility and are highly selective for known inhibitors over drug-like non-inhibitors
analysis
study of protein dynamics, using a pump-probe method that employs pulsed-laser photothermal heating of a gold nanoparticle (AuNP) to directly excite a local region of the protein structure and transient absorbance to probe the effect on enzyme activity. Activity is accelerated by pulsed-laser excitation when the AuNP is attached close to a network of coupled motions in DHFR. No rate acceleration is observed when the AuNP is attached away from the network with pulsed excitation, or for any attachment site with continuous wave excitation
biotechnology
in vivo screening system to select for functionally active proteins with increased solubility. Fusion of enzyme to green fluorescent protein as reporter for solubility
biotechnology
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method for screening combinatorial or other libraries of enzyme based on affinities of the inhibitors with the enzyme
biotechnology
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method for screening combinatorial or other libraries of Plasmodium falciparum enzyme based on affinities of the inhibitors with the enzyme
drug development
enzyme is identical to enzyme from Bacillus anthracis. Use of enzyme as antimicrobial target for Bacillus anthracis, homology modelling of inhibitors and growth inhibition assays
drug development
enzyme is identical to enzyme from Bacillus cereus. Use of enzyme from Bacillus cereus as antimicrobial target for Bacillus anthracis, homology modelling of inhibitors and growth inhibition assays
drug development
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comparison of Danio rerio and human enzyme to evaluate the suitability of the fish enzyme as an assay system for antifolate drug discovery. Structural and kinetic proterties of both enzymes are similar and susceptibilites to known inhibitors are also comparable
drug development
comparison of Danio rerio and human enzyme to evaluate the suitability of the fish enzyme as an assay system for antifolate drug discovery. Structural and kinetic proterties of both enzymes are similar and susceptibilities to known inhibitors are also comparable
drug development
expression of bifunctional dihydrofolate reductase-thymidylate synthase in plasmodium falciparum to assess interaction with antifolates
drug development
modeling of 31 pyrimethamine derivatives into the active site of dihydrofolate reductase obtained from crystal structures 1J3I.pdb and 1J3K.pdb. Evaluation of predicted binding modes and key protein-ligand interactions
drug development
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modeling of 32 pyrimethamine derivatives into the active site of dihydrofolate reductase obtained from crystal structure 1J3K.pdb. Evaluation of predicted binding modes and key protein-ligand interactions
drug development
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receptor-based pharmacophore models based on ensembles of protein conformations from molecular dynamics simulations of enzyme in complex with NADPH in both the closed and open conformation of the M20 loop. Optimal models identify enzyme inhibitors over druglike noninhibitors. Model performance improves with increased dynamic sampling
drug development
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use of multiple protein structure technique for structure-based drug discovery. Construction of receptor-based pharmacophores using multiple X-ray crystallographic structures. Models incorporate a fair degree of protein flexibility and are highly selective for known inhibitors over drug-like non-inhibitors
drug development
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use of multiple protein structure technique for structure-based drug discovery. Construction of receptor-based pharmacophores using multiple X-ray crystallographic structures. Models incorporate a fair degree of protein flexibility and are highly selective for known inhibitors over drug-like non-inhibitors
drug development
DHFR is a valid drug target
drug development
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mtDHFR is an attractive target for the development of anti-tuberculosis drugs
drug development
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the enzyme is a possible target for treatment of cryptosporidiosis caused by the organism
drug development
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the enzyme is a target for antifolate drugs. The parasite develops resistance to several used antifolates via mutations in the active site, e.g. point mutations of residues Ala16, Ile51, Cys59, Ser108 and Ile164, overview
drug development
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the enzyme is a target for drug development since the organism causes the opportunistic infection Pneumocystis pneumonia, a major cause of mortality in acquired immunodeficiency syndrome, AIDS, patients
drug development
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the enzyme is a target for drug development since the organism causes the opportunistic infection toxoplasmosis, a major cause of mortality in acquired immunodeficiency syndrome, AIDS, patients
drug development
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the enzyme is a target for inhibitor design, overview
drug development
the essential enzyme is a target for development of specific inhibitors
drug development
the essential enzyme is a target for development of specific inhibitors for treatment of the biodefense organism Bacillus anthracis
drug development
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the essential enzyme is a target for development of specific inhibitors for treatment of the causative agent in AIDS pneumonia
drug development
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the essential enzyme is a target for development of specific inhibitors for treatment of the causative agent in AIDS pneumonia
drug development
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dihydrofolate reductase is a potential drug target for the elimination of Brugia malayi, one of the three causative agents of lymphatic filariasis, a parasitic disease
drug development
enzyme DHFR is an important drug target
drug development
the enzyme is a target for drug development in the treatment of Human African trypanosomiasis (HAT), an infectious disease caused by two distinct subspecies of the protozoan parasite Trypanosoma brucei subsp. gambiense and Trypanosoma brucei subsp. rhodesiense
drug development
the enzyme is an anti-parasitic drug target, e.g. for malaria or human cancers, because rapidly growing cells require folate to produce thymine
drug development
the enzyme represents an attractive target for inhibitor design to disrupt systems that require rapid DNA turnover, e.g. proliferating cancer cells and pathogenic microbes
drug development
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the enzyme is a target for drug development in the treatment of Human African trypanosomiasis (HAT), an infectious disease caused by two distinct subspecies of the protozoan parasite Trypanosoma brucei subsp. gambiense and Trypanosoma brucei subsp. rhodesiense
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medicine
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drug target
medicine
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potentially target for the discovery of novel insecticides and anthelminthics
medicine
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biomarker, key target in chemotherapy
medicine
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enzyme is a target of several anti-folate inhibitory drugs to combat bacteria, protozoa and cancer
medicine
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enzyme is a target of several anti-folate inhibitory drugs to combat bacteria, protozoa and cancer
medicine
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enzyme is a target of several anti-folate inhibitory drugs to combat bacteria, protozoa and cancer
medicine
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enzyme is a target of several anti-folate inhibitory drugs to combat bacteria, protozoa and cancer
medicine
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enzyme is a target of several anti-folate inhibitory drugs to combat bacteria, protozoa and cancer
medicine
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enzyme is a target of several anti-folate inhibitory drugs to combat bacteria, protozoa and cancer
medicine
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enzyme is a target of several anti-folate inhibitory drugs to combat bacteria, protozoa and cancer
medicine
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enzyme is a target of several anti-folate inhibitory drugs to combat bacteria, protozoa and cancer
medicine
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enzyme is a target of several anti-folate inhibitory drugs to combat bacteria, protozoa and cancer
medicine
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enzyme is a target of several anti-folate inhibitory drugs to combat bacteria, protozoa and cancer
medicine
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enzyme is a target of several anti-folate inhibitory drugs to combat bacteria, protozoa and cancer
medicine
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enzyme is a target of several anti-folate inhibitory drugs to combat bacteria, protozoa and cancer
medicine
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sequence analysis of enzyme isolated from strains in different regions of India. Prevalence of double enzyme mutants and some with triple mutants in isolates from mainland, presence of qudruple mutants in isolates from Car Nicobar Island. Association between the degree of malaria transmission and the number of enzyme mutations
medicine
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a 19-bp deletion polymorphism is not associated with overall breast cancer risk, although a borderline significant additive interaction between the dihydrofolate reductase genotype and multivitamin use is observed. Multivitamin supplements may place a subgroup of women, i.e., those with the19-bp allele, at elevated risk of developing breast cancer. A dose-dependent relation between dihydrolfolated reductase expression and the 19 bp deletion genotype is observed
medicine
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analysis of intronic 19-bp deletion polymorphism and two polymorphisms within the 3' untranslated region as candidates for risk of neural tube defect. The 829C>T polymorphism is not found to be variable within the Irish population. The 19-bp intron deletion and the 721A>T polymorphisms are found to be in linkage disequilibrium. The 19-bp intron deletion allele shows a significant protective effect in mothers of neural tube defect cases when present in one or two copies
medicine
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analysis of polymorphisms among 129 isolates from different geographical areas in India. A gradual increase in the frequency of mutant genotypes is observed from north to south, while isolates from the Car-Nicobar islands show only mutant genotypes
medicine
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analysis of the impact of the dihydrofolate reductase c.86 + 60_78 insertion/deletion polymorphism on folate and homocysteine concentrations. Among men the polymorphism is not signficantly associated with serum or red blood cell folate concentrations, or with homocysteine concentrations. Among women the polymorphis mexplains 2% of the variation in red blood cell folate levels and 5% of the variation in serum folate levels, but does not appear to have an independent effect on homocysteine
medicine
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c-Myc oncoprotein protein level is elevated in cervical intraepithelial neoplasia 1, cervical intraepithelial neoplasia 2, cervical intraepithelial neoplasia 3 biopsies. Concomitantly, dihydrofolate reductase gene amplification is detected. The degrees of dihydrofolate reductase gene amplification and of c-Myc protein levels are a measure of the progressive degree of the lesion
medicine
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Double knock-out lines of bifunctional dihydrofolate reductase-thymidylate synthase are unable to infect mice, whereas the virulence of single knock-out lines is similar to wild-type
medicine
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identification of synonymous and non-synonymous single nucleotide polymorphisms in the Plasmodium vivax dihydrolfolate reductase gene isolated from patients from Colombia, India, Indonesia, Papua New Guinea, Sri Lanka, thailand, and Vanuatu. The double mutant 58R/117N allele has evolved from several origins, because the 58R is encoded by at least 3 different codons. The triple 58R/61M/117T and quadruple 57L/61M/117T/173F, 57I/58R/61M/117T and 57L/58R/61M/117T mutant alleles had at least three independent origins in Thailand, Indonesia, and Papua New Guinea/Vanuatu
medicine
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in 451 blood samples from Plasmodium vivax cases in Sri Lanka, 68.9% showed dihydrofolate reductase wild-type haplotype. The double mutant F57L/S58R haplotype was the most frequently observed mutant with 24.4%, while the triple mutant F57L/S58R/S117N was only identified once. A significantly higher frequency of mutant haplotypes is observed in the Northern districts
medicine
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in a total of 92 Plasmodium falsiparum-infected blood samples from children in Mozambique, the frequency of the sulphadoxine/pyrimethamine resistance-associated dihydrofolate reductase triple mutants 51I/59R/108N and of dihydrofolate reductase /dihydropteroate synthetase quintuple mutants 51I/59R/108N + 437G/540E was 93% and 47%, respectively. However, no dihydrolfolate reductase 164L mutants were detected
medicine
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in clinical samples, a worse outcome is associated with increased levels of dihydrofolate reductase and C-MYC at diagnosis in osteosarcoma patients treated with a methotrexate-based protocol and of C-MYC in patients treated with a standard four-drug regimen. The assessment of C-MYC and dihydrolfolate reductase at diagnosis, together with that of other known prognostic markers, can be considered for an early identification of subgroups of OS patients with higher risk of adverse outcome
medicine
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in parasites isolated from Sudanese patients treated with sulphadoxine/pyrimethamine or sulphadoxine/pyrimethamine plus chloroquine, mutations have been detected in dihydrofolate reductase at N51I, S108N, and C59R, plus mutations in dihydropteroate synthetase. There is no significant correlation between multiplicity of mutation and response to sulphadoxine/pyrimethamine
medicine
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knock-down of dihydrofolate reductase or heart and neural crest derivatives expressed transcript HAND2 in fertilized eggs causes cardiac malformation. Expression of HAND2 is reduced in dihydrofolate reductase knock-down embryos. Microinjection of HAND2 mRNA into fertilized eggs can induce HAND2 overexpression which rescues the cardiac malformation phenotypes of dihydrofolate knock-down embryos
medicine
renal ischemia-reperfusion decreases dihydrofolate reductase mRNA and protein levels, both of which are restored by angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker, whereas GTP-cyclohydrolase 1 expression is unaltered. Renal ischemia-reperfusion suppresses endothelial nitric oxide synthase dimer while enhancing the monomer and augments inducible nitric oxide synthase mRNA, total inducible nitric oxide synthase protein and monomer, which are attenuated by angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker
medicine
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screening for the 19-bp deletion and the 9-bp repeat in dihydrolfolate reductase gene of 121 mothers of a spina bifida affected child, 109 spina bifida patients, 292 control women and 234 pediatric controls. The 19-bp del/del genotype is not associated with spina bifida risk in mothers and children and both the WT/del and the del/del genotype do not aVect expression relative to the WT/WT genotype. The 9-bp repeat is not associated with spina bifida risk in mothers and children. Expression of the 6/6 allele is 73% increased compared to the 3/3 allele, although not significantly
medicine
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study on Plasmodium falciparum isolates from 118 children in Cote d'Ivoire. 39.5% are highly resistant to pyrimethamine, with IC50 values above 2000 nM. 39% of the isolates have mutant dihydrofolate reductase and 94% mutant dihydropteroate synthetase genes, and mutant dihydrofolate reductase is associated with resistance to pyrimethamine in vivo and in vitro
medicine
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study on prevalence and frequency of dihydrofolate reductase and dihydropteroate synthetase mutations associated with sulfadoxine-pyrimethamine resistance at surveillance sites in Southern Mozambique. Frequency of dihydrofolate triple mutation increased from 0.26 in 1999 to 0.96 in 2003, remaining high in 2004. Parasites with both dihydrofolate reductase triple mutation and dihydropteroate synthetase double mutations had increased in 2001, but decreased by 2004. The peaking of sulfadoxine-pyrimethamine resistance markers in 2001 coincided with a sulfadoxine-pyrimethamine resistant malaria epidemic in neighboring regions
medicine
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study on the association between the clinical and parasitological response to sulfadoxinepyrimethamine and allelic combinations of dihydrofolate reductase and dihydropteroate synthase genes. Determination of dihydrofolate reductase and dihydropteroate synthase genotypes is of limited value to predict the treatment outcome in individual patients, mostly due to few treatment failures and few wild-type haplotypes. The majority of clinical isolates is characterized as quadruple, i.e. 196 isolates with mutations N51I-C59R-S108N in dihydrofolate reductase and A437G dihydropteroate synthase, or triple mutants, i.e. 97 isolates with mutations N51I-C59R-S108N in dihydrofolate reductase and wild-type dihydropteroate synthase, or S108N + N51I or C59R in dihydrofolate reductase and A437G in dihydropteroate synthase. Wild-type, single mutation, and double mutation were observed in 29, 20, and 13 parasites, respectively
medicine
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study on the association of polymorphisms in dihydrofolate reductase gene and treatment response in children with acute lymphoblastic leukemia. Lower event-free survival is associated with homozygosity for the allele A-317 and C-1610, and with the haplotype *1, and mRNA analysis shows higher dihydrofolate reductase levels for haplotype *1 carriers
medicine
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study on the effect of co-trimoxazole prophylaxis on Plasmodium falciparum antifolate resistance development among HIV-infected persons. Mutation I164L is not associated with high-level sulfadoxine-pyrimethamine resistance or poor outcome among adults living where malaria is highly endemic
medicine
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the naturally occurring single nucleotide polymorhism C829T, near the miR-24 binding site in the 3' UTR of human dihydrofolate reductase leads to a decrease in microRNA binding, which in turn leads to overexpression of its target and results in resistance to methotrexate
medicine
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the prevalence of dihydrofolate reductase 19-bp deletion polymorphism and of the methylenetetrahydrofolate reductase C677T polymorphism is similar in cancer patients with and without thrombosis. The frequency of factor V Leiden polymorphism is significantly higher in cancer patients with thrombosis. Thus routine screening for dihydrofolate reductase 19-bp deletion polymorphism is not suggested
medicine
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target for therapy of acute lymphoblastic leukemia
medicine
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significantly reduced inflammatory responses and mortality are observed in zebrafish infected with Staphylococcus aureus pre-incubated with grape seed extract. Grape seed extract might serve as an effective natural alternative for the control of food poisoning caused by Staphylococcus aureus with proper safety measure
medicine
amplification of a DHFR gene from field isolate PKNY146CSP collected from Southern Thailand. Aanalysis shows 11 polymorphisms in the DHFR domain of the bifunctional DHFR-TS gene. One polymorphism is a non-synonymous substitution (R34L) that has been reported but not associated with antifolate resistance
medicine
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amplification of a DHFR gene from field isolate PKNY146CSP collected from Southern Thailand. Aanalysis shows 11 polymorphisms in the DHFR domain of the bifunctional DHFR-TS gene. One polymorphism is a non-synonymous substitution (R34L) that has been reported but not associated with antifolate resistance
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synthesis
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develoment of a method for bacterial expression of mouse translation factor eIF4E tagged with mutant dihydrofolate reductase. Recombinant eIF4E and DHFR-eIF4E both show to significantly enhance in vitro translation in dose dependent manner by 75% at 0.0005 mM. Increased concentrations of eIF4E and DHFR-eIF4E significantly inhibit translation in a dose dependent manner by a maximum at 0.0022 mM of 60% and 90%, respectively
synthesis
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the use of the dihydrofolate-reductase-targeted short hairpin RNA vector can enhance the IgG expression in the gene-amplified stable CHO cells and uphold the IgG expression in methotrexate-free cultures
synthesis
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transformation of murine dihydrofolate reductase cDNA by a series of nested PCRs to reproduce the amino acid coding sequence for bovine DHFR, which differs from the murine sequence by 19 amino acids. Expression of the bovine dihydrofolate reductase cDNA in bacterial cells produces a stable recombinant protein with high enzymatic activity and kinetic properties similar to those previously reported for the native protein
synthesis
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transformation of murine dihydrofolate reductase cDNA by a series of nested PCRs to reproduce the amino acid coding sequence for bovine DHFR, which differs from the murine sequence by 19 amino acids. Expression of the bovine dihydrofolate reductase cDNA in bacterial cells produces a stable recombinant protein with high enzymatic activity and kinetic properties similar to those previously reported for the native protein
synthesis
application of HEK-293 cells as an alternative host cell line for stable expression of therapeutic glycoproteins. DHFR-deficient cells are generated by disrupting both DHFR and DHFR1 in HEK-293E cells and an expression vector containing DHFR and monoclonal antibody gene is transfected into the disruption mutant. A stable high-producing recombinant HEK293 cell line can be established using DHFR/methotrexate-mediated gene amplification
synthesis
folate production by the mutant L62F in two-stage fermentation process with temperature shift-up from 30°C to 40°C increases by three-fold compared with the parental strain