29 results about "Deoxyuridine" patented technology

The invention discloses a synthesis method of 2 '-fluoro-2'-deoxyguanosine. According to the method, thymine nucleoside phosphorylase and purine nucleoside phosphorylase are used as biocatalysts, and 2 '-fluoro-2'-deoxyuridine and guanine are used as substrates to synthesize the 2 '-fluoro-2'-deoxyguanosine. Compared with a chemical method, the production cost is greatly reduced; meanwhile, the synthesis method can effectively solve the problem that the product is difficult to separate.

The invention discloses a reagent and a method for improving the tolerance of a PCR inhibitor and application, and belongs to the technical field of molecular biology. According to the invention, the thermosensitive uracil DNA glycosidase and the deoxyuridine triphosphate are combined and used as the PCR antiinhibitor to be applied to DNA amplification of a whole blood sample, and experiments prove that the composition can improve the endurance capacity of a PCR reaction system to a whole blood inhibitor, reduce the false negative rate and improve the accuracy and reliability of detection. Meanwhile, the method for carrying out PCR reaction by using the composition is simple to operate, low in cost and high in nucleic acid detection sensitivity. Therefore, the reagent and the method have a good application prospect in detection of nucleic acid extracted from a whole blood sample.

The invention discloses pyridine DPP fluorophore extension type deoxyuridine as well as a preparation method and application thereof, and belongs to the field of biological medicine and detection. The invention provides a uridine analogue modified by a fluorescent chromophore DPP derivative with a structure shown in the specification, and pyridine DPP fluorophore extension type deoxyuridine has excellent fluorescent property, can be used as a fluorescent probe, and is widely applied to the fields of biochemistry, medicine and the like.

To provide a method for producing 5-fluoro-2' - deoxyuridine-5' -O - [1-naphthyl (benzyloxy-L-alaninyl)] phosphate (NUC-3373) and a method for producing 3' - deoxyadenosine-5' -O - [phenyl (benzyloxy-L-alaninyl)] phosphate (NUC-7738).SOLUTION: A compound of Formula (IIa) or (IIb) is reacted with a compound of Formula (IIIa) or (IIIb), respectively, in presence of a base (B1) and the protecting groups are removed from the resulting compound of Formula (IVa) or (IVb) to provide NUC-3373 or NUC-7738.SELECTED DRAWING: None

The invention discloses a method for rapidly detecting MTHFR (Methylene Tetrahydrofolate Reductase) gene polymorphism based on a complementary probe technology, which comprises the following steps: S1, acquiring a sample: extracting genome DNA (Deoxyribose Nucleic Acid) from a sample to be detected as an amplification template; s2, preparing a reaction system: adding the genome DNA, the upstream primer, the downstream primer, the C probe, the T probe, uracil-N-glycosylase, DNA polymerase, deoxyribonucleoside triphosphate and deoxyuridine triphosphate of the sample to be detected into the reaction system; s3, carrying out PCR (Polymerase Chain Reaction) amplification reaction under the conditions that the temperature is 90-98 DEG C, and the time is 5-20 minutes; performing denaturation at the temperature of 90-98 DEG C for 10-50 seconds; the temperature is 55-69 DEG C, and annealing is conducted for 60-120 s; the temperature is 68-72 DEG C, and extension is carried out for 15-300 s; carrying out 35 to 40 cycles; and S, genotype judgment. A test result is the same as a first-generation sequencing test result, which shows that the detection method of the scheme has relatively high accuracy. Meanwhile, compared with a sequencing method, the method has the advantages that a series of complex follow-up treatment does not need to be carried out on a PCR product, PCR amplification and detection are synchronously carried out, the detection time is greatly shortened, and the detection cost is reduced.

The embodiment of the invention provides a connecting unit for chemical modification of a nucleic acid terminal group, a solid-phase carrier and a preparation method of the solid-phase carrier, the chemical modification comprises N-acetylgalactosamine, and the method comprises the following steps: mixing L-deoxyuridine with iodine, and carrying out iodine substitution reaction to obtain 8-iodine-L-deoxyuridine; carrying out triphenyl methylation on the 8-iodine-L-deoxyuridine to protect 5 '-terminal hydroxyl, carrying out palladium catalytic coupling reaction to obtain 8-alkenyl-L-deoxyuridine ester compounds, and hydrolyzing to obtain unsaturated carboxyl modified L-deoxyuridine derivatives; the unsaturated carboxyl modified L-deoxyuridine derivative and N-acetylgalactosamine are subjected to condensation, and the connecting unit for nucleic acid end group chemical modification is obtained. The connection unit obtained by the method has better enzymolysis resistance, and the synthesis method is simple and efficient.

The invention discloses a drug delivery nano system based on ROS response as well as a preparation method and application of the drug delivery nano system. The drug delivery nano system comprises nanoparticles and a camptothecin-5-fluorodeoxyuridine prodrug, wherein the nanoparticles are formed by self-assembly of an amphiphilic high-molecular polymer HA-IR-780 with a photosensitive characteristic, and the camptothecin-5-fluorodeoxyuridine prodrug is wrapped in the nanoparticles; and the surface of the drug delivery nano system is modified with a lipid-polyethylene glycol material. When the drug delivery nano-system is applied to preparation of breast cancer drugs, the drug delivery nano-system can be enriched at a tumor site depending on the passive targeting effect of the EPR effect of the drug delivery nano-system, breast cancer chemotherapy / PDT / PTT / combined treatment can be achieved, and the effects of reducing toxicity and enhancing efficacy are achieved to a certain extent.

The application discloses a monomerized pyrimidine nucleoside phosphorylase mutant and a construction method and application thereof, and belongs to the field of enzyme engineering and biological catalysis technology.The mutant is obtained by amino acid substitution mutation of wild-type pyrimidine nucleoside phosphorylase shown in SEQ ID NO:1, and the amino acid sequence is shown in SEQ ID NO:2.The mutant is transformed into a stable monomer form by dimer interface remodeling and hinge region stabilization of the closed active conformation, the natural dimer PyNP is transformed into a stable monomer form, and the catalytic activity of the mutant to uridine, 2'-deoxyuridine and similar substrates is maintained in the monomer state.Compared with the wild-type enzyme, the mutant has lower oligomer dependence, better temperature stability, pH stability and storage stability, and can be used for biological catalytic synthesis of nucleosides and nucleoside analogs.

The invention relates to a hydantoin-containing deoxyuridine triphosphatase inhibitor and a preparation method thereof. Provided herein are dUTPase inhibitors, compositions comprising these compounds, and methods of using these compounds or compositions.

Described herein are synthetic methods for producing sequence-specific RNA oligonucleotides that eliminate impurities produced in prior art methods. In one aspect, a first amplification primer includes one or more deoxyuridine residues, wherein at least one of the one or more deoxyuridine residues is at position −1, −2, −3, −4 or −5 of the promoter region for the single-subunit, DNA-dependent RNA polymerase. The deoxyuridines are excised to provide an amplified functional template DNA which is then used to synthesize RNA which has reduced immunogenic double stranded RNA compared to controls.

The present disclosure provides pyrimidine nucleoside compounds, including torcitabine, thymidine, deoxyuridine, deoxycytidine and uridine, and methods to treat telomere biology disorders (TBDs) and aging-related diseases, including hematological disorder, liver disease, or hepatic fibrosis, comprising administering to a subject diagnosed with said telomere biology disorder a therapeutically effective amount of said compounds.

The invention discloses a fluorodeoxyuridine monophosphate prodrug as shown in a formula I, application of the prodrug in preparation of a medicine for treating liver cancer, a pharmaceutical composition containing the prodrug and pharmaceutically acceptable auxiliary materials or taraxasterol and application of the prodrug in preparation of the medicine for treating liver cancer, and belongs to the field of pharmacy. The compound is modified by specific natural amino acid residues and can be used for preparing medicines for treating liver cancer. The in-vitro and in-vivo anti-tumor activity of the compound is remarkably superior to that of the prior art, the compound has a synergistic effect when being combined with taraxasterol, the highest tumor inhibition rate reaches 91.72%, the compound is high in selectivity, good in safety and high in liver targeting performance, and a more effective new scheme is provided for liver cancer treatment.

The invention discloses a heterologous transport protein YdhP and application thereof in production of beta-thymidine from escherichia coli, and belongs to the technical field of microbial engineering. According to the present invention, by introducing the heterologous transport protein ydhP derived from Ralstania mannitolyticus, the extracellular secretion of beta-thymidine can be effectively promoted, and the intracellular feedback regulation limitation can be reduced; during shake flask fermentation, the yield of beta-thymidine is increased to 1.6 g / L (increased by about 45%), and the by-product deoxyuridine is reduced by about 50%; the yield in a 5 L fermentation tank reaches 20 g / L, which is obviously improved compared with that of a control strain (12 g / L), and an efficient and stable engineering strain and a fermentation process are provided for industrial production of beta-thymidine.

The present invention relates generally to the fields of cancer cell biology, cancer therapeutics for cancers located within in the central nervous system, thymidine analogs and cellular nucleotide excision repair mechanisms. More specifically, the invention relates to the use of EdU in methods of treating cancers located within in the central nervous system, and methods of inhibiting and / or reducing growth of a cancer or cancer cell.

The invention discloses a bithiophene DPP derivative modified deoxyuridine as well as a synthesis method and application thereof, and belongs to the field of biological medicine and detection. The invention provides a bithiophene DPP derivative modified deoxyuridine shown in the following structure, and the compound has excellent fluorescent property, can be used as a fluorescent probe, and is widely applied in the fields of biochemistry, medicine and the like. The target product is directly generated, and other reactions such as glycosylation and hydrolysis are avoided. The method has the characteristics of relatively simple and controllable reaction conditions, no generation of by-products, high yield and the like.

The application discloses a reagent, a method and application for improving PCR inhibitor tolerance, and belongs to the technical field of molecular biology. The application combines heat-sensitive uracil DNA glycosylase and deoxyuridine triphosphate, and applies the combination as a PCR anti-inhibitor in DNA amplification of a whole blood sample. Experiments prove that the combination can improve the tolerance of a PCR reaction system to whole blood inhibitors, reduce the false negative rate, and improve the accuracy and reliability of detection. Meanwhile, the method for performing PCR reaction by using the combination is simple in operation, low in cost, and high in nucleic acid detection sensitivity. Therefore, the reagent and the method have good application prospects in the detection of nucleic acids extracted from a whole blood sample.

The invention relates to a method of producing cladribine with a purity greater than 99.9 wt.% from 2-deoxyuridine and 2-chloroadenine by using the catalytic action of high concentrations (at least 20.000 U / L) of freely dissolved transglycosidases UP (uridine phosphorylase) and PNP (purine nucleoside phosphorylase) in an enzymatic synthesis in an aqueous environment without the presence of any organic solvent.

The invention relates to the technical field of biology, in particular to a preparation and purification method of 2 '-fluoro-2'-deoxyguanosine. The invention discloses a preparation and purification method of 2 '-fluoro-2'-deoxyguanosine.The preparation method comprises the following steps that 2, 6-diaminopurine and 2 '-fluoro-2'-deoxyuridine generate 2 '-fluoro-2, 6-diaminopine-2'-deoxynucleoside under the catalysis of thymine nucleoside phosphorylase and purine nucleoside phosphorylase, filtering is conducted, and the 2 '-fluoro-2, 6-diaminopine-2'-deoxyguanosine is obtained. Then adenosine deaminase is added for catalysis, and 2 '-fluoro-2'-deoxyguanosine is generated; biosynthesis of the 2 '-fluoro-2'-deoxyguanosine is divided into two stages, the intermediate 2 '-fluoro-2, 6-diaminopine-2'-deoxynucleoside is synthesized firstly, and then deamination is performed to form the 2 '-fluoro-2'-deoxyguanosine, so that the problem that the conversion rate is extremely low when guanine with low solubility is taken as a substrate is solved.

According to the invention, an amplification-free, high-sensitivity and high-specificity monomolecular biosensing platform is constructed. According to the single-molecule biosensing platform, the clickchemistry-based multi-fluorophore nucleic acid probe is designed and synthesized by taking DNA (Deoxyribose Nucleic Acid) of orientia tsutsugamushi as a model target. 5-ethynyl-2 '-deoxyuridine triphosphate is introduced into the probe through a polymerase chain reaction, so that the probe carries a plurality of alkynyl modification sites and is further connected with a large number of Cy5 fluorophores, signals are greatly enhanced, and the photobleaching problem is effectively relieved. Meanwhile, random optical reconstruction microscopy is introduced to serve as a detection reading mode, the random flicker characteristic of fluorescent molecules is utilized, tens of thousands of single molecule events are positioned and counted, and signals are further amplified. The application successfully develops a simple, rapid, high-sensitivity and high-specificity single-molecule detection platform, provides an effective tool for the detection of low-abundance biomarkers, and has wide application prospects in the fields of early diagnosis of diseases and the like.

The application relates to the technical field of deoxyuridine intermediate synthesis, and specifically discloses a new type of 2'-methoxy uridine compound containing 4'-methyl or 4'-alkynyl and a synthesis method thereof. The synthesis method of the new type of 2'-methoxy uridine compound containing 4'-methyl or 4'-alkynyl comprises the following steps: taking 2'-methoxy uridine as raw material to synthesize an intermediate 9 containing two TBSO groups; the intermediate 9 is subjected to an oxidation reaction, a Seyferth-Gilbert carbon increase reaction and TBSO group deprotection to obtain an intermediate 12; the intermediate 9 is reacted with thiophosgene phenyl ester, then methyl intermediate 14 is generated under the condition of TMSS and AIBN, and then the TBSO group deprotection is carried out to obtain an intermediate 15; the new type of 2'-methoxy uridine compound containing 4'-methyl or 4'-alkynyl provided by the application can be used for the synthesis of a drug intermediate and the research on biological activity, and has the advantages of high product stability.

The invention describes a method of the enzymatic synthesis of cordycepin and its 2-halogen derivatives by reacting 3 -deoxyuridine with adenine or its 2-halogen derivatives in an aqueous phosphate reaction medium under the catalytic action of uridine phosphorylase (UP) and purine nucleoside phosphorylase (PNP). The synthetic method according to the invention is fast, technologically and energetically undemanding and environmentally friendly, and does not require the presence of organic solvents or chromatographic purification of pure cordycepin, while being easily transferable to laboratory and mass production conditions.

The invention discloses a method for detecting iodo-nucleoside in drinking water through solid-phase extraction-vacuum centrifugal concentration-liquid chromatography-tandem mass spectrometry, which comprises the following steps: enriching target substances in the drinking water by using solid-phase extraction, and then concentrating a sample by using a vacuum centrifugal concentrator, and finally, determining the concentrations of 2-iodine adenosine, 8-iodine adenosine, 5-iodine cytidine, 8-iodine guanosine, 5-iodine uridine, 6-iodine uridine, 2-iodine-2 '-deoxyadenosine, 5'-iodine-5 '-deoxyadenosine, 5-iodine-2'-deoxycytidine, 5-iodine-2 '-deoxyuridine, 2'-iodine-2 '-deoxyuridine and 5'-iodine-5 '-deoxyguanosine by using a multi-reaction monitoring mode of liquid chromatography tandem mass spectrometry. According to the method disclosed by the invention, the detection technologies of solid-phase extraction, vacuum centrifugal concentration and high performance liquid chromatography-tandem mass spectrometry are combined, so that the detection of trace iodo-nucleoside under a complex matrix condition is realized; the method has the advantages of low detection limit, high sensitivity, short detection time and the like.

The embodiment of the invention provides a connecting unit for chemical modification of a nucleic acid terminal group, a solid-phase carrier and a preparation method of the solid-phase carrier, the chemical modification comprises N-acetylgalactosamine, and the method comprises the following steps: mixing L-deoxyuridine with iodine, and carrying out iodine substitution reaction to obtain 8-iodine-L-deoxyuridine; carrying out triphenyl methylation on the 8-iodine-L-deoxyuridine to protect 5 '-terminal hydroxyl, carrying out palladium catalytic coupling reaction to obtain 8-alkenyl-L-deoxyuridine ester compounds, and hydrolyzing to obtain unsaturated carboxyl modified L-deoxyuridine derivatives; the unsaturated carboxyl modified L-deoxyuridine derivative and N-acetylgalactosamine are subjected to condensation, and the connecting unit for nucleic acid end group chemical modification is obtained. The connection unit obtained by the method has better enzymolysis resistance, and the synthesis method is simple and efficient.

The present invention relates to phosphoramidate prodrugs (phosphoramidate derivatives of nucleosides), in particular phosphoramidate prodrugs for use in the treatment of cancer, the present invention relates to pharmaceutical formulations and formulation strategies for use in pharmaceutical formulations, e.g., NUC-3373 (5-fluoro-2 '-deoxyuridine-5'-O-[1-naphthyl (benzyloxy-L-alanyl)] phosphate) and NUC-7738 (3 '-deoxyadenosine-5'-O-[phenyl (benzyloxy-L-alanyl)] phosphate), for example, NUC-3373 (5-fluoro-2 '-deoxyuridine-5'-O-[1-naphthyl (benzyloxy-L-alanyl)] phosphate). In particular, the present invention relates to formulations comprising a polar aprotic solvent, such as dimethylacetamide (DMA).

The invention describes a method of the enzymatic synthesis of cordycepin and its 2-halogen derivatives by reacting 3 -deoxyuridine with adenine or its 2-halogen derivatives in an aqueous phosphate reaction medium under the catalytic action of uridine phosphorylase (UP) and purine nucleoside phosphorylase (PNP). The synthetic method according to the invention is fast, technologically and energetically undemanding and environmentally friendly, and does not require the presence of organic solvents or chromatographic purification of pure cordycepin, while being easily transferable to laboratory and mass production conditions.

Provided are methods and formulations for the treatment of p53-deficient cancers using a combinational drug strategy which enhances DNA damage in p53 deficient cells while not allowing cells to escape cell death by activation of p53-p21 signaling. Wild-type p53 carriers, on the other hand, respond with activation of p53-p21 signaling and cell-cycle arrest, thereby escaping cell death. The methods involve administering to an individual in need of treatment a combination of one or more poly (ADP ribose) polymerase inhibitors (PARPi) and one or more deoxyuridine analogs. Pharmaceutical formulations comprising PARPi and dU analogs are also provided.

The present invention relates to phosphoramidate prodrugs (phosphoramidate derivatives of nucleosides), in particular phosphoramidate prodrugs for use in the treatment of cancer, the present invention relates to pharmaceutical formulations and formulation strategies for use in pharmaceutical formulations, e.g., NUC-3373 (5-fluoro-2 '-deoxyuridine-5'-O-[1-naphthyl (benzyloxy-L-alanyl)] phosphate) and NUC-7738 (3 '-deoxyadenosine-5'-O-[phenyl (benzyloxy-L-alanyl)] phosphate), for example, NUC-3373 (5-fluoro-2 '-deoxyuridine-5'-O-[1-naphthyl (benzyloxy-L-alanyl)] phosphate). In particular, the present invention relates to formulations comprising a polar aprotic solvent, such as dimethylacetamide (DMA).

This invention belongs to the field of biotechnology and relates to a nucleoside monomer chemically modified with exogenous functional groups and a covalent nucleic acid aptamer containing the same nucleoside monomer. The nucleoside monomer contains exogenous functional group chemical modifications, including deoxyuridine phosphorimide and phosphate thioester modifications; the nucleoside monomer includes Sgc8c; the base sequence of Sgc8c is shown in SEQ ID No. 1. Based on the existing nucleic acid aptamer Sgc8c that binds to PTK7, it is chemically modified into a covalent aptamer. A covalent aptamer is an aptamer modified with a covalently reactive target that can specifically bind to a target protein and undergo a proximity-mediated covalent reaction to form a covalent complex. The covalent aptamer can convert the non-covalent complex of a conventional aptamer with a target protein into a covalent complex, thereby preventing rapid dissociation and withstanding various environmental stresses, thus exerting a long-term and stable biological function.