Search results for "Folate"
showing 10 items of 110 documents
Quinazoline antifolate thymidylate synthase inhibitors: replacement of glutamic acid by aminophosphonic acids
2003
The synthesis of six analogues of the potent thymidylate synthase (TS) inhibitor N -[4-[ N -[(3,4-dihydro-2-methyl-4-oxo-6-quinazolinoyl)-methyl]- N -prop-2-ynylamino]benzoyl]- L -glutamic acid 2 is described in which the glutamic acid residue has been replaced by DL -aminophosphonic acids. New antifolates were tested as inhibitors of TS isolated from mouse L1210 leukemic cells as well as inhibitors of growth mouse leukemic L5178Y cells. In general these modifications result in compounds that are considerably less potent than 2 as TS inhibitors with K i 's 0.17-1.10 w M. Very poor solubility in water limited their proper assay of growth cells inhibition.
A Novel 68Ga-Labeled Pteroic Acid-Based PET Tracer for Tumor Imaging via the Folate Receptor
2012
The folate receptor (FR) is a very attractive target in oncological imaging as it is overexpressed by a variety of cancer types, whereas the expression in healthy tissue is very limited. The synthesis of regioisomeric pure folic acid derivatives normally requires a regioselective approach and does not allow the use of native folic acid (FA). As the pharmacophore of FA is assumed to be pteroic acid, its use without the glutamic acid moiety may enable the possibility to considerably simplify the synthesis of a positron emission tomography (PET) tracer for FR imaging. In this work, DO3A-EA-Pte was successfully synthesized and labeled with 68Ga. It is stable for up to 3 h in PBS and against tra…
Target Analogue Imprinted Polymers with Affinity for Folic Acid and Related Compounds
2001
Two approaches to synthesize molecularly imprinted polymers with affinity for folic acid and other substituted pteridines have been compared. In the first approach, the folic acid analogue methotrexate was used as template and functional monomers capable of generating selective binding sites were searched in a miniaturized screening system based on binding assessment in the batch mode. Highest selectivity was seen using 2-vinylpyridine as functional monomer, which was confirmed in the chromatographic mode for a batch synthesized on a gram scale. However, the retentivity and selectivity of this phase were insufficient for anticipated applications. In a second approach, using methacrylic acid…
Why Are Some Enzymes Dimers? Flexibility and Catalysis in Thermotoga maritima Dihydrofolate Reductase
2019
[Image: see text] Dihydrofolate reductase from Thermotoga maritima (TmDFHFR) is a dimeric thermophilic enzyme that catalyzes the hydride transfer from the cofactor NADPH to dihydrofolate less efficiently than other DHFR enzymes, such as the mesophilic analogue Escherichia coli DHFR (EcDHFR). Using QM/MM potentials, we show that the reduced catalytic efficiency of TmDHFR is most likely due to differences in the amino acid sequence that stabilize the M20 loop in an open conformation, which prevents the formation of some interactions in the transition state and increases the number of water molecules in the active site. However, dimerization provides two advantages to the thermophilic enzyme: …
Loss of Hyperconjugative Effects Drives Hydride Transfer during Dihydrofolate Reductase Catalysis
2019
Hydride transfer is widespread in nature and has an essential role in applied research. However, the mechanisms of how this transformation occurs in living organisms remain a matter of vigorous debate. Here, we examined dihydrofolate reductase (DHFR), an enzyme that catalyzes hydride from C4′ of NADPH to C6 of 7,8-dihydrofolate (H2F). Despite many investigations of the mechanism of this reaction, the contribution of polarization of the π-bond of H2F in driving hydride transfer remains unclear. H2F was stereospecifically labeled with deuterium β to the reacting center, and β-deuterium kinetic isotope effects were measured. Our experimental results combined with analysis derived from QM/MM si…
Eating patterns are associated with biomarkers in a selected population of university students and employees.
2011
AbstractThe association between diet and CVD cannot be assigned to a single nutrient, but rather to a set of nutrients and non-nutrients, and eating pattern analyses have become an important tool in investigation of this relationship. Our objective was to investigate eating patterns in relation to nutrient intake and serum concentration of folate, vitamin B12 and TAG in ninety-five healthy adult participants. Dietary information was collected by an FFQ, and eating patterns were obtained by principal components analyses of thirty-three food groups. Three eating patterns were extracted, a sweet eating pattern identified by intakes of cakes, snacks, sugar-sweetened drinks and chocolates; a pru…
The efficacy and safety of nutrient supplements in the treatment of mental disorders: a meta‐review of meta‐analyses of randomized controlled trials
2019
The role of nutrition in mental health is becoming increasingly acknowledged. Along with dietary intake, nutrition can also be obtained from "nutrient supplements", such as polyunsaturated fatty acids (PUFAs), vitamins, minerals, antioxidants, amino acids and pre/probiotic supplements. Recently, a large number of meta-analyses have emerged examining nutrient supplements in the treatment of mental disorders. To produce a meta-review of this top-tier evidence, we identified, synthesized and appraised all meta-analyses of randomized controlled trials (RCTs) reporting on the efficacy and safety of nutrient supplements in common and severe mental disorders. Our systematic search identified 33 me…
Morphology and Progression in Primary Varicose Vein Disorder Due to 677C>T and 1298A>C Variants of MTHFR
2015
Background: Clinical assessment and prognostic stratification of primary varicose veins have remained controversial and the molecular pathogenesis is unknown. Previous data have suggested a contribution of the MTHFR (methylenetetrahydrofolate reductase) polymorphism c.677C>T. Methods: We collected blood and vein specimens from 159 consecutive patients undergoing varicose vein surgery, or autologous vein reconstruction for arterial occlusive disease as controls. We compared the frequencies of c.677C>T and another polymorphism of MTHFR, c.1298A>C, with morphology and types of complicated disease. Morphology was recorded as a trunk or perforator type and peripheral congestive complication was …
Cell Uptake Enhancement of Folate Targeted Polymer Coated Magnetic Nanoparticles
2013
Dual targeted drug delivery systems represent a potential platform for developing efficient vector to tumor sites. In this study we evaluated a folate- and magnetic-targeted nanocarriers based on 10 nm iron oxide nanodomais coated with the properly synthesized and characterized folic acid (FA)-functionalized amphiphilic copolymer PHEA-PLA-PEG-FA. FA was chemically conjugated to one end of diamino-polyethylene glycol of 2000 Da, in order to ensure its exposition on the polymer coated magnetic nanoparticles (MNPs-FA). The prepared nanoparticles have been exhaustively characterized by different methods, including DLS, SEM, FT-IR and magnetic measurements. Magnetic nanoparticles showed dimensio…
Effects of polymorphisms in endothelial nitric oxide synthase and folate metabolizing genes on the concentration of serum nitrate, folate, and plasma…
2015
Abstract Objectives A number of studies have explored the effects of dietary nitrate on human health. Nitrate in the blood can be recycled to nitric oxide, which is an essential mediator involved in many important biochemical mechanisms. Nitric oxide is also formed in the body from l -arginine by nitric oxide synthase. The aim of this study was to investigate whether genetic polymorphisms in endothelial nitric oxide synthase (eNOS) and genes involved in folate metabolism affect the concentration of serum nitrate, serum folate, and plasma total homocysteine in healthy individuals after folic acid supplementation. Methods In a randomized double-blind, crossover study, participants were given …