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Showing 1 to 20 of 26 for “"thymidylate synthase"”.
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Computational and Pharmacological Approaches to Design Novel Allosteric Thymidylate Synthase Inhibitors
… of this research is to develop new allosteric thymidylate synthase (TS) inhibitors in an effort to reduce cancer drug resistance. Resistance is associated with elevation in TS levels upon exposure to active site targeted drugs. Human TS exists in conformational equilibrium between active and …
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DNA Damage and Cell Death Mediated by Thymidylate Synthase Inhibitors: Role of UNG and SMUG1 DNA Glycosylase
… to its active metabolites that inhibits thymidylate synthase (TS), thus depriving cells of thymidylate and subsequently increasing the uracil (U) content. Alternatively, 5-FU metabolites can also cause DNA damage by direct incorporation into DNA or RNA. Incorporation of U and 5-FU …
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Molecular Dissection of the Ubiquitin-Independent Degradation Signal At the Unstructured Amino Terminal End of Human Thymidylate Synthase
… substrates is the human DNA metabolic enzyme thymidylate synthase (TS). Previous studies showed that the degradation of TS is mediated by an intrinsically disordered 27-residue region at the N-terminal end of the protein, and that this region, in cooperation with an alpha-helix formed by the …
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Interactions between Folate Deficiency and β-Nicotinamide Adenine Dinucleotide Deficiency and Conformational Study of Thymidylate Synthase and its Physiological Relevance
… <p><strong>Part II:</strong></p> <p>Thymidylate synthase (TS) catalyzes the reaction that forms dTMP from dUMP. Previous data suggested that human thymidylate synthase (hTS) exists in two major conformations, active and inactive. Two hTS mutants were created to mimic the active and …
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The Mechanism of N10-Formyltetrahydrofolate Synthetase. Use of Human Thymidylate Synthase Variants to Characterize Asymmetric Ligand Binding and to Identify Novel Allosteric Inhibitors.
… fixation, and purinolysis, through the glycine synthase/reductase pathway. The formation of fTHF occurs via a two-step process, which involves the formation of a formylphosphate (XPO) intermediate. The XPO intermediate has been proposed based on kinetic and spectroscopic experiments and …
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Design and synthesis of pyrimido[4,5-b]indoles and furo[2,3-d]pyrimidines as single agents with combination chemotherapy potential or as inhibitors of tubulin or thymidylate synthase
… agents that disrupt microtubule dynamics. Thymidylate synthase (TS) inhibitors prevent cell division by interfering with de novo thymidylate synthesis. Antiangiogenic agents target tumor angiogenesis crucial for tumor growth and metastasis. Under normal circumstances, angiogenesis is …
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Replacement of Val3 In Human Thymidylate Synthase Affects Its Kinetic Properties and Intracellular Stability, Complexes of Sperm Whale Myoglobin G65T With Phenol and Ethylene Glycol, and Structure of A Fragment of Human End-Binding Protein 1 (Eb1)
<p>CHAPTER 1: REPLACEMENT OF VAL3 IN HUMAN THYMIDYLATE SYNTHASE (HTS) AFFECTS ITS KINETIC PROPERTIES AND INTRACELLULAR STABILITY.</p> <p>Human and other mammalian thymidylate synthase (TS) enzymes have an N-terminal extension of about 27 amino acids which is not present in bacterial TSs. The …
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Design and Synthesis of Pyrimidine Based Heterocycles as Potential Anti-cancer Agents with Combination Chemotherapeutic Potential or Targeted One Carbon Metabolism Inhibition and Anti-opportunistic Agents
… for inhibition of tubulin polymerization or thymidylate synthase as well as for inhibition of one or more of the receptor tyrosine kinases (RTKs)- vascular endothelial growth factor receptor-2 (VEGFR2), epidermal growth factor receptor (EGFR) and/or platelet-derived growth factor receptor β …
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Synthesis of Bicyclic Thieno[2,3-d]Pyrimidines, Tricyclic Thieno[2,3-d]Pyrimidines and Thieno[3,2-d]Pyrimidines as Classical and Nonclassical Antifolates
… agents has been reviewed and discussed. Thymidylate synthase (TS), dihydrofolate reductase (DHFR) and glycinamide ribonucleotide formyltransferase (GARFTase) are important folate dependent enzymes that are targets for cancer chemotherapy and the treatment of infectious diseases. As a part …
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Genetic Association Study of Osteoporotic Vertebral Compression Fractures in Postmenopausal Women
… reductase (MTHFR) and thymidylate synthase (TS) are involved in homocysteine metabolism. Thus, we determined whether or not VEGF, MTHFR, and TS polymorphisms are associated with osteoporotic vertebral compression fractures in postmenopausal Korean women. The study …
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Study of the Cryptosporidium parvum DHFR-TS in the model system Saccharomyces cerevisiae
… bifunctional DHFR-TS (dihydrofolate reductase-thymidylate synthase) enzyme and an engineered monofunctional DHFR domain alone. Yeast reliant on the DHFR-TS form show the expected synergy between trimetrexate, a DHFR inhibitor, and sulfanilamide, an inhibitor of dihydropteroate synthase (DHPS), …
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Expression of Bax Predicts Outcome in Advanced Gastric Cancer Patients Treated With 5-fluorouracil and Platinum Palliative Chemotherapy
… cross-complementation group 1 (ERCC1), and thymidylate synthase (TS) on clinical outcomes in patients with advanced gastric cancer treated with 5-fluorouracil (5-FU) and platinum palliative chemotherapy. Materials and Methods: One hundred and twenty-eight patients with metastatic or …
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Synthesis of furo[2,3-d]pyrimidines, thieno[2,3- d]pyrimidines, pyrrolo[2,3-d]pyrimidines as classical and nonclassical antifolates, receptor tyrosine kinase (RTK) inhibitors and antimitotic agents
… and anti mitotic agents has been discussed. Thymidylate synthase (TS), dihydrofolate reductase (DHFR) and glycinamide ribonucleotide formyltransferase (GARFTase) are important folate dependent enzymes that are targets for cancer chemotherapy and the treatment of infectious diseases. Classical …
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The Structural Distribution of Epistasis in a Pair of Essential Metabolic Enzymes
… pathway, Dihydrofolate Reductase (DHFR) and Thymidylate Synthase (TYMS). To achieve this goal, I used deep mutational scanning assays on DHFR in the context of varying activities of TYMS. The result is a rigorous dataset with epistasis measurements over the entire amino acid sequence of DHFR. …
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Synthesis and Molecular Modeling Studies of Bicyclic Inhibitors of Dihydrofolate Reductase, Receptor Tyrosine Kinases and Tubulin
… (pjDHFR) and T. gondii (tgDHFR)</p><p> 2. Thymidylate synthase: human (hTS) and T. gondii (tgTS)</p><p> 3. Receptor tyrosine kinases: VEGFR2, EGFR and PDGFR-β</p><p> 4. Colchicine binding site of tublulin.</p><p> Novel homology models were generated and validated for pjDHFR, tgDHFR, tgTS, …
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Information retrieval and mining in high dimensional databases
… pertaining to RNA-directed DNA Polymerase and Thymidylate Synthase, and use the motifs to classify the proteins. Then we apply the method to clustering chemical compounds pertaining to aromatic, bicyclicalkanes and photosynthesis. Experimental results indicate the good performance of our …
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Design and Synthesis of Pyrimidine Based Fused Heterocyclics in the Potential Treatment of Cancer and Opportunistic Infection
… due to mutagenesis in the target enzyme (thymidylate synthase). This dissertation focuses on the development of substituted-pyrazolo[4,3-<em>d</em>]pyrimidines and pyrrolo[2,3-<em>d</em>]pyrimidines to combat the above-mentioned drawbacks of PMX, using the X-ray crystal structures of …
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Target Based Design and Synthesis of Fused Pyrimidines in the Potential Treatment of Cancer and Opportunistic Infection
… strains expressing mutated dihydropteroate synthase enzyme (target of SMX). For patients unresponsive or resistant to this treatment, newer drugs are critically needed. The absence of an X-ray crystal structure of pjDHFR poses a large gap in drug discovery efforts. The status quo, as it …
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