Global ETD Search
Search theses and dissertations gathered from participating repositories worldwide. Every result links back to the library that holds it. No account is needed.
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Showing 1 to 18 of 18 for “"Nitroreductase"”.
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The synthesis and study of novel fluorescence probes for Nitroreductase
… photophysical characteristics and response to nitroreductase (NTR) in a biological setting. Chapter 3 explores synthetic modifications to the compounds described in Chapter 2 in order to increase NTR sensitivity. A set of novel fluorescence sensors are described where the sensitivity is …
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Oncolytic adenovirus vectors for nitroreductase suicide gene therapy of prostate cancer
… the E1B-55K deletion and expressed the transgene nitroreductase for combined oncolytic virotherapy and enzyme/prodrug gene therapy. The latter of these two vectors, vNR6, expressing nitroreductase from the pIX virus promoter demonstrated the greatest cytotoxicity at low virus concentrations …
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A Computational Investigation of the Mechanism of CB1954 Reduction by E.coli Nitroreductase
The flavoenzyme NTR (nitroreductase nfsB from Escherichia coli) and the prodrug CB1954 (5-[aziridin-1-yl]-2,4-dinitrobenzamide) have been found to be a good potential combination for virus-directed enzyme prodrug therapy (VDEPT). However, wild-type NTR has poor kinetics and binding with CB1954, and …
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Fluorogenic probes for live-cell imaging of biomolecules
… for drugs or other cargos. Chapter 4. Paired Nitroreductase-Probe System to Quantify the Cytosolic Delivery of Biomolecules. Cytosolic delivery of large biomolecules is a significant barrier to therapeutic applications of CRISPR, RNAi, and biologics such as proteins with anticancer properties. …
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Synthetic Materials with Redox-Triggers for Imaging and Drug Delivery
… caged probe released active methylene blue by nitroreductase-mediated 1,6-elimination resulting exhibition of strong fluorescence (λmax = 680 nm) with the excitation at 580 nm. The fluorescence emission was also induced by incubation with live escherichia coli bacteria. It was demonstrated that …
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Studies on nucleotide levels and electron transport genes of Clostridium acetobutylicum P262
… strain Fl9. F19 was shown to have diminished nitroreductase activity, which was presumed to be responsible for the metronidazole resistant phenotype. However, the recA mutation renders E. coli F19 highly susceptible to the reduced toxic intermediates of metronidazole. The E. coli F19 recA, …
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Investigating the resistance that arises in Escherichia coli towards the furazolidone – vancomycin antibiotic combination : Master of Science (Biological Sciences) at Massey University, Manawatū, New Zealand
… These mutations were found to result in a lower nitroreductase activity, predominantly affecting the key nitrofuran-activating nitroreductases NfsA and NfsB.
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Nitroaromatic pro-drug activation and resistance in the African trypanosome
… activity. Here, the role of the bacterial-like nitroreductase TbNTR as a nitrodrug activating enzyme is examined through overexpression and knock-out studies in T. brucei. Multiple attempts to purify soluble recombinant TbNTR from E. coli were unsuccessful, because the recombinant protein was …
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Use of a direct, positive selection strategy to generate improved prodrug-activating enzymes for cancer gene therapy
E. coli NfsB nitroreductase (NTR) is currently being studied in combination with the prodrug CB1954, as a gene directed enzyme prodrug therapy. NTR reduces CB1954 at either the 2- or 4-nitro groups to produce highly cytotoxic hydroxylamine derivatives, using either NADH or NADPH as cofactor. …
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Analogues of Nitrofuran Antibiotics are Potent GroEL/ES Pro-drug Inhibitors with Efficacy against Enterococcus Faecium, Staphylococcus Aureus, and Escherichia Coli
… effective GroEL/ES inhibitors when E. coli NfsB nitroreductase was introduced into the GroEL/ES-dMDH refolding assay, metabolizing the nitro groups to their active species. Importantly, lead analogs that potently inhibited bacterial growth exhibited low cytotoxicity to human colon and intestine …
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Targeted gene therapy for canine osteosarcoma: preliminary investigations
… perform suicide gene/prodrug assays using nitroreductase (NTR) in combination with CB1954 or nitrofurazone (NFZ) in several canine cell lines; replace luciferase with NTR in vectors for TP53-targeted suicide gene strategy, and with CB1954, determine if survival of CMT7 cells possessing …
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Plant Activation of Bicyclic Aromatic Amines, Benzidine and 4-Aminobiphenyl
… activation of benzidine and 4-ABP, and bacterial nitroreductase is partially involved in the mutagenic activation in Salmonella typhimurium. The mutagenic plant-activated benzidine and 4-ABP metabolites were fractionated using ultrafiltration membrane separation. The mutagenic metabolites were …
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Role of macrophages in larval zebrafish heart regeneration
… macrophage-less irf8-/- larvae and metronidazole-nitroreductase macrophage ablation to test the requirement for macrophages for several important regenerative processes. My data showed macrophages to be required for wound debridement and cardiomyocyte proliferation but not structural and …
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Development of tumour imaging and therapy strategies utilising unengineered bacteria
… system than those that are currently in use. The nitroreductase (NTR) enzymes, found only in bacteria, represent one such option. Chapter 2 introduces the novel concept of utilising native bacterial NTRs for the targeted activation of the fluorophore CytoCy5S. Bacterial-mediated probe activation …
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Small Molecule and Macromolecular Donors of Reactive Sulfur Species: Insights into Reactivity and Therapeutic Potential
… responded to the bacteria-specific enzyme nitroreductase to release its persulfide payload. NDP-NAC elicited gastroprotective effects in mice that were not observed in animals treated with control compounds incapable of persulfide release or in animals treated with Na2S. NDP-NAC induced …
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Charakterisierung neuer Zielstrukturen für die Antibiotikatherapie gegen Staphylococcus aureus und Entwicklung eines konditionalen In-vivo-Expressionssystems
Bislang inhibieren antibakterielle Substanzen in erster Linie die Zellwandsynthese, den DNA- und RNA-Stoffwechsel sowie die Proteinsynthese. In dieser Arbeit wurde ein erster Versuch unternommen, neue Zielstrukturen für die Antibiotika-Therapie in S. aureus zu finden. Insgesamt wurden 10 Gene …
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Investigation of a fusogenic pH-sensitive liposomal system for tumour-targeted intracellular delivery of dinitrobenzamide mustard prodrugs
… line (EMT6) transfected with a DNBMactivating nitroreductase gene (nfsB). IC50 values were compared with nPSL-SN25860 and free drug. Cytotoxicity was tested at extracellular pH (pHex) representative of normal tissues (pHex 7.4) and poorly perfused regions of tumours (pHex 6.5). Cytotoxicity of …