56 results about "Deoxyguanosine" patented technology

The invention discloses application of a small molecule compound in prevention and treatment of plant RNA virus infection, and belongs to the technical field of biology. According to the invention, 2 '-amino-2'-deoxyguanosine (ADG) is used as a unique antiviral active component to be applied to prevention and treatment of plant RNA viruses for the first time, and broad-spectrum inhibition of various plant RNA viruses such as turnip mosaic virus (TuMV), tomato mosaic virus (ToMV) and tobacco mosaic virus (TMV) can be realized only by a low concentration of 250 [mu] M and a simple exogenous spraying mode; and after spraying, the normal growth of plants is not influenced, the risk of phytotoxicity is thoroughly avoided, the safety, high efficiency and broad spectrum of plant RNA virus prevention and control are remarkably improved, and important practical application significance is achieved for guaranteeing the yield and quality of crops in agricultural production and promoting agricultural green transformation.

The invention relates to the field of environmental chemistry and biological sample analysis, in particular to an analysis method for detecting oxidative stress biomarkers in urine. The analysis method capable of simultaneously detecting dityrosine, 8-hydroxyguanosine, 8-hydroxydeoxyguanosine and 4-hydroxynonenal mercaptouric acid in human urine is provided on the basis of liquid chromatography-tandem mass spectrometry, effective purification of a urine sample is achieved through specific pretreatment, the matrix effect is reduced, and the detection sensitivity is improved. And specific liquid chromatogram parameter conditions are combined, so that simultaneous detection of the four oxidative stress biomarkers is realized. The method is good in selectivity, high in sensitivity and high in detection speed, the problem that polar and non-polar components cannot be measured at the same time at present is solved, the contained oxidative stress biomarkers are more comprehensive and more reasonable, and the oxidative stress damage condition of the organism can be better reflected.

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.

This invention provides a method for the simultaneous and rapid detection of four oxidative stress-related biomarkers and its application. The detection method includes: (S1) pretreatment of samples using a protein precipitation extract to simultaneously extract four target compounds: 8-hydroxydeoxyguanosine, 8-isoprostaglandin F2β, 8-isoprostaglandin F2α, and acetyllysine, and preparing a test solution; the protein precipitation extract is a methanol-acetonitrile-perchloric acid mixed solution containing formic acid, wherein the volume ratio of methanol, acetonitrile, and perchloric acid is (8-10):(8-10):(0.5-1), and the volume concentration of formic acid is 0.1-0.5%; (S2) detection of the test solution and standard solution using liquid chromatography-tandem mass spectrometry, and matrix calibration using an internal standard method; plotting a standard curve with the peak area ratio of the target compound to the internal standard as the ordinate and the concentration as the abscissa; and calculating the concentration of the target compound in the test solution based on the standard curve.

The invention discloses an application of halogenase in catalytic synthesis of 2 '-halogenated nucleoside. The halogenase is any one of NSH1, NSH2, NSH3, NSH4 and NSH5, and a substrate used for catalysis is any one of 2 '-deoxyguanosine, 2'-deoxyinosine and 2 '-deoxyadenosine. The biosynthesis method provided by the invention has the advantages of high reaction stereoselectivity, high product yield, simple halogen source, easily controlled operation process, low production cost, green and environment-friendly reaction, high catalytic activity and the like, and a new method is provided for synthesis of the 2 '-halide.

An oligonucleotide molecule has 10 to 50 nucleotides that include at least one G-quartet forming motif having 10 to 20 nucleotide residues. At least 60% of the residues of the G-quartet forming motif are guanosine or deoxyguanosine residues. The oligonucleotide molecule inhibits tumor growth and / or viral or bacterial replication and / or exerts anti-inflammatory effects in mammalian cells.

This invention relates to the fields of environmental chemistry and biological sample analysis, specifically to an analytical method for detecting oxidative stress biomarkers in urine. Based on liquid chromatography-tandem mass spectrometry (LC-MS / MS), this invention provides an analytical method for the simultaneous detection of dityrosine, 8-hydroxyguanosine, 8-hydroxydeoxyguanosine, and 4-hydroxynonenal mercaptouric acid in human urine. This method achieves effective purification of urine samples through specific pretreatment, reducing matrix effects, and, combined with specific LC parameters, enables the simultaneous detection of four oxidative stress biomarkers. This method exhibits good selectivity, high sensitivity, and fast detection speed, solving the current problem of the inability to simultaneously determine polar and nonpolar components. It includes a more comprehensive and rational list of oxidative stress biomarkers, better reflecting the body's oxidative stress damage.

Compositions and methods relating to a pharmacological therapy for a human genetic disease, specifically mitochondrial DNA depletion-deletions syndromes, and more specifically, those related to mutations in the GUK1 gene. The pharmacological therapy involves the administration of deoxyguanosine (dG), a purine nucleoside phosphorylase (PNP) inhibitor, including but not limited to forodesine, or both.

The invention relates to the technical field of nephritis medicine, in particular to an AAGN disease metabolism marker, a kit and application of the AAGN disease metabolism marker. In the blood or urine metabolism marker, the blood metabolism marker is prepared from one or more of 6-methyl nicotinamide, hypo-sulphosarcosine, guanosine, allopurinol, 8-hydroxy-2 '-deoxyguanosine, triglyceride or lysophosphatidylcholine; the urine metabolism markers comprise one or more of D-malic acid, leucyl-alanyl-valine, N-hydroxymethyl nicotinamide, DL-tribulus terrestris alkali, isoxotrexate, 1, 3-dimethyluric acid, leucyl-leucyl-phenylalanine, alloandrosterone, enterodiphenol and p-coumarin, and the urine metabolism markers comprise one or more of D-malic acid, leucyl-alanyl-valine, N-hydroxymethyl nicotinamide, DL-tribulus terrestris alkali, isoxotrexate, 1, 3-dimethyluric acid, leucyl- The metabolic marker combination and the kit are used for evaluating the disease activity state of a patient suffering from ANCA-related glomerulonephritis (AAGN), and have good repeatability, stability and biological correlation.

The present invention discloses a method for preparing 2'-deoxyguanosine, guanosine and a composition thereof, and uses thereof, which belong to the technical field of controlling pathogenic microorganisms, specifically, the use of 2'-deoxyguanosine and guanosine in inhibiting Vibrio parahaemolyticus in marine fish farming, the use of 2'-deoxyguanosine and guanosine in anti-plant viruses, and the use of 2'-deoxyguanosine and guanosine in improving the content of 2'-deoxyguanosine, guanosine and salicylic acid in plants. The present invention provides a composition containing 2'-deoxyguanosine and guanosine, and a method for extracting 2'-deoxyguanosine and guanosine from Paecilomyces variotii SJ1 fungus. The present invention has found that 2'-deoxyguanosine and guanosine have an effect of controlling pathogenic microorganisms, in particular, a remarkable anti-plant virus effect, and can also improve the contents of 2'-deoxyguanosine, guanosine, and salicylic acid in plants.

The invention provides a 2 '-fluoro-2'-deoxyguanosine crystal form II and a preparation method thereof. The 2 '-fluoro-2'-deoxyguanosine crystal form substance provided by the invention is a low hydrate, has the advantages of good crystal form stability, no hygroscopicity, large bulk density, large particles, good fluidity, stable quality and easy storage, is used for downstream production without dehydration treatment, and has high efficiency and high synthesis yield. The crystallization method of the 2 '-fluoro-2'-deoxyguanosine crystal form II is simple and easy to implement, high in crystallization yield, high in purity and suitable for commercial production.

The invention discloses a siRNA molecule targeting a human SLC25A17 gene, the siRNA molecule comprises a positive-sense strand and an antisense strand, the specific sequence is as follows: the positive-sense strand: 5 '-CCUUGGAUGUGUUCAUCAUNn-3', the antisense strand: 5 '-AUGAUGAACACAUCAAGGNn-3', N in the positive-sense strand and N in the antisense strand are the same or different, and are respectively and independently cytosine C, uracil U, guanine G, adenine A, deoxycytosine dC, deoxyguanine dG, deoxyadenine dA or deoxythymine dT; n represents the number of N, and n = 0, 1 or 2. The invention further discloses application of the siRNA molecule of the targeted human SLC25A17 gene, and the siRNA molecule is applied to liver cancer treatment by efficiently inhibiting the expression level of SLC25A17.

The application discloses a method for purifying and chromatographing and mass spectrometrically identifying deoxyguanosine or 3-hydroxybenzoic acid and application. After metabolites are extracted by a methanol method, UPLC-MS / MS-ultra high performance liquid chromatography and ABSCIEX QTRAP 5500 triple quadrupole tandem linear ion trap mass spectrometry are used to distinguish the metabolites by using liquid chromatography and mass spectrometry. The MS technology provides the ability to detect and quantify a large number of metabolites. The method optimizes the purification and mass spectrometric identification of the progeria markers in blood, identifies the structures of the differential markers deoxyguanosine and 3-hydroxybenzoic acid in blood by using the mass spectrometric method, and distinguishes the difficult-to-distinguish differential markers. The method for purifying and mass spectrometrically identifying the progeria differential markers in blood is simple and easy to operate, has small experimental dosage, good stability, is fast and accurate, and can make up for the deficiency in searching for the blood differential markers.

The invention relates to a nanofiber vaccine combined medicine and application thereof. The combined medicine comprises a first preparation and a second preparation, the first preparation is 6-thio-2 '-deoxyguanosine; the second preparation is a nanofiber vaccine, and the nanofiber vaccine comprises an E744-62-Q11 nanofiber vaccine or a Q11-M30 nanofiber vaccine; the invention relates to an E744-62-Q11 nanofiber vaccine, which is formed by connecting a synthesized self-folding peptide Q11 and an HPV16E7 antigen peptide through gene fusion and self-assembling in vitro, the invention relates to a Q11-M30 nanofiber vaccine, which is formed by self-assembling a synthesized self-folding peptide Q11 and a mouse melanoma B16-F10 tumor antigen M30 in vitro. The invention finds that THIO has a direct regulation effect on a key immunosuppressive cell MDSC, and reveals that THIO can directly down-regulate tumor immunosuppression and remodel a tumor microenvironment; the THIO and the nanofiber vaccine are combined for use, the tumor cell specific killing and TME regulation potential of the THIO is disclosed, the THIO and a tumor vaccine stimulate effector cell response to generate a synergistic anti-tumor effect, and a new strategy is provided for combined immunotherapy for inducing tumor ICD based on the THIO.

The present invention belongs to the technical field of DNA synthesis. Provided is a method for synthesizing an N2-C6 amino-modified deoxyguanosine monomer. The synthesis method comprises: performing a silylation protection reaction on deoxyguanosine under the protection of a silanization reagent so as to obtain a first intermediate; performing a Mitsunobu reaction on a second reaction raw material to obtain a second intermediate; performing a nucleophilic substitution reaction on the first intermediate and the second intermediate to obtain a third intermediate; and performing a desilylation protection reaction and a protective group introduction reaction, followed by an activation coupling reaction to obtain a final product. In the synthesis method, the final product is prepared by performing the silylation protection reaction, the Mitsunobu reaction, the nucleophilic substitution reaction, the protective group introduction reaction and the activation coupling reaction on the raw materials. The synthesis method has the advantages of the chemical raw materials used being simple and readily available, and being low cost; having mild reaction conditions, and easy to scale-up production; high stability of the intermediate obtained; and being a simple purification method and easily operated.

The application discloses a kind of solid phase extraction-liquid quality connection simultaneously detecting multiple nucleotides in drinking water in the technical field of water pollution monitoring, first using solid phase extraction enrichment target material, nitrogen blow concentration, finally using the concentration of guanosine acid, adenosine acid, cytidine acid, uridine acid, deoxyguanosine acid, deoxyadenosine acid, deoxycytidine acid and deoxythymidine acid is determined using the multiple reaction monitoring mode of liquid chromatography tandem mass spectrometry, the present application combines solid phase extraction pretreatment technology with the detection technology of liquid chromatography tandem mass spectrometry, realizes the detection of trace nucleotide under complex matrix condition, the present application can realize the simultaneous determination of multiple nucleotides by one sample injection, with the advantages of high recovery rate, short detection time, many detection types and the like.

To provide a method for non-invasive evaluation of an aging degree of skin.SOLUTION: A method for non-invasive evaluation of an aging degree of skin includes the steps of: 1) applying a solvent-containing three-dimensional structure having a liquid retaining property and a liquid releasing property to skin; 2) collecting the solvent in the three-dimensional structure to obtain an extraction liquid; 3) concentrating the extraction liquid; and 4) measuring an amount of 8-hydroxy deoxyguanosine in the concentrated liquid; wherein the measured amount of 8-hydroxy deoxyguanosine is used as an indicator.SELECTED DRAWING: None

The present invention provides an eye drop preparation in the form of an aqueous solution containing 8-oxo-2'-deoxyguanosine or a pharmaceutically acceptable salt thereof, a thickener, a buffer, and a chelating agent in an aqueous medium, the eye drop preparation having a viscosity of 10 to 30 mPa s. The eye drop preparation of the present invention exhibits an appropriate retention time in the eye and exhibits excellent stability without forming precipitates even when stored for a long period of time.

The invention provides a urine metabolism marker combination for distinguishing kidney benign diseases and kidney cancer and application of the urine metabolism marker combination, and belongs to the technical field of biomarkers. The urine metabolism marker combination for distinguishing the kidney benign disease from the kidney cancer comprises at least two of the following components: (S)-2-piperidine-6-carboxylic acid, 2 '-deoxyguanosine, 3-hydroxybutyric acid, 6-aminocaproic acid, glycyl-L-proline, glycyl-gamma-aminobutyric acid, L-cysteine sulfinic acid and N, N-dimethyl formamide. The amino acid sequence is shown in the specification, and the amino acid sequence is shown in the specification. The amino acid sequence is shown in the specification, namely, N, N-dimethyl glycine, N-acetyl-L-glutamic acid, L-methionine-L-aspartic acid, 2-oxoglutaric acid and glycine chenodeoxycholic acid. Model construction and verification analysis show that the AUC values of diagnosis models constructed by combining different quantities of metabolite markers are all greater than 0.8, the sensitivity is greater than 0.7, and the specificity is greater than 0.7. Therefore, based on the urine metabolism marker combination screened by the invention, the kidney benign disease and the kidney cancer can be efficiently and accurately distinguished.

The present invention provides a novel 2'-deoxyguanosine derivative or a pharmaceutically acceptable salt thereof, a preparation method therefor, a pharmaceutical composition comprising same, and use thereof. The 2'-deoxyguanosine derivative or a pharmaceutically acceptable salt thereof can be effectively applied to the prevention and treatment of corneal damage due to various causes.

The disclosure provides, inter alia, oligonucleotides comprising 6-thio-2′-deoxy-guanosine residues. The oligonucleotides comprising said residues are used in pharmaceutical compositions and methods for treating cancer. The invention also includes CpG oligodeoxynucleotides in combination with the 6-thio-2-deoxy-guanosine residues in said pharmaceutical compositions and methods for treating cancer. Oligonucleotides of the invention may also include additional therapeutic moieties or exonuclease resistant moieties. The compositions and methods of the invention may employ additional pharmaceutical entities for the treatment of cancer.

Disclosed herein are telomere-targeting phosphatidyl-thio conjugates comprising nucleoside analogs 6-thio-2'-deoxyguanosine and 6-thioguanosine, that target telomers in cancer cells as well as pharmaceutical compositions thereof, and therapeutic methods for the administration of a therapeutically effective amount of the telomere-targeting phosphatidyl-thio conjugate compounds to treat cancers, such as colorectal cancer, non-small cell lung cancer and hepatocellular cancer.

This invention discloses a purification method for 2'-fluoro-2'-deoxyguanosine, belonging to the field of biomedical technology, comprising the following steps: subjecting crude 2'-fluoro-2'-deoxyguanosine containing 2,6-diaminopurine and uracil impurities to an acetylation reaction to generate diacetylated 2'-fluoro-2'-deoxyguanosine, which is then separated; subjecting the diacetylated 2'-fluoro-2'-deoxyguanosine to a deacetylation reaction to obtain crude 2'-fluoro-2'-deoxyguanosine, which is then purified by pulping to obtain high-purity 2'-fluoro-2'-deoxyguanosine. This invention utilizes a combined process of "acetylation-deacetylation-pulping" to obtain 2'-fluoro-2'-deoxyguanosine with a purity of over 99%. Employing widely available and inexpensive raw materials and a simple chemical reaction pathway, it provides a method for effectively removing 2,6-diaminopurine and uracil without column chromatography. This process has promising prospects for industrial scale-up.

The present invention provides methods for producing crystalline anti-PD-1 monoclonal antibodies (mAbs), wherein the mAbs are pembrolizumab or pembrolizumab variants, comprising (1) mixing a solution comprising (a) a mAb, (b) polyethylene glycol (PEG), and (c) an additive selected from the group consisting of caffeine, theophylline, 2'-deoxyguanosine-5'-monophosphate, a biologically active gibberellin, and a pharmaceutically acceptable salt of the biologically active gibberellin to form a crystallization solution; (2) incubating the crystallization solution for a time sufficient for crystal formation; and (3) optionally harvesting the crystalline anti-PD-1 mAb from the solution. In particular embodiments, the PEG is PEG 3350, and the additive is caffeine. The present invention also relates to novel anti-human PD-1 mAb crystals produced by the methods described herein. Characterization of the resolubilized crystal suspensions using several biochemical methods indicates that the biophysical properties of the resolubilized mAb crystals are consistent with the intact antibody starting sample. The crystals and methods of the present invention are suitable for a variety of pharmaceutical applications, such as purification, storage, formulation, and drug delivery.

The invention provides methods for producing crystalline an anti-PD-1 monoclonal antibody (mAb), wherein the mAb is pembrolizumab or a pembrolizumab variant, comprising (1) mixing a solution comprising (a) the mAb, (b) polyethylene glycol (PEG), and (c) an additive selected from the group consisting of: caffeine, theophylline, 2′ deoxyguanosine-5′-monophosphate, a bioactive gibberellin, and a pharmaceutically acceptable salt of said bioactive gibberellin, to form a crystallization solution, (2) incubating the crystallization solution for a period of time sufficient for crystal formation; and (3) optionally harvesting the crystalline anti-PD-1 mAb from the solution. In specific embodiments, the PEG is PEG 3350 and the additive is caffeine. The invention also relates to the novel anti-human PD-1 mAb crystals produced by the methods described herein. Characterization of re-dissolved crystalline suspensions using several biochemical methods showed the bio-physical properties of the re-dissolved mAb crystals were consistent with the intact antibody starting sample. The crystals and methods of the invention are amenable to multiple pharmaceutical applications such as purification, storage, formulation, and drug delivery.

The application discloses a diabetic nephropathy diagnosis biomarker and application thereof, and belongs to the field of in-vitro diagnosis, wherein the diabetic nephropathy diagnosis biomarker is a combination of 8-hydroxydeoxyguanosine and nitrate; the concentration of 8-hydroxydeoxyguanosine and nitrate in urine can be detected by a double-antibody enzyme-linked immunoassay and a nitric oxide analyzer respectively, and then a diabetic nephropathy diagnosis scheme based on the two biomarkers is constructed; the scheme has the advantages of non-invasiveness and high specificity, can accurately distinguish diabetic nephropathy from diabetes, and provides a new strategy for early screening and diagnosis of diabetic nephropathy.

An anti-8-OHdG antibody and an antibody fragment thereof, with which 8-hydroxy-2′-deoxyguanosine (8-OHdG) in a specimen, particularly urine, can be accurately analyzed, and a measuring method capable of measuring 8-OHdG in a specimen, particularly urine, with high sensitivity are provided. An anti-8-OHdG antibody or an antibody fragment thereof which reacts specifically with 8-OHdG and substantially does not react with urea; the antibody or antibody fragment thereof in which the complementarity-determining regions of the variable regions of heavy and light chains are specific amino acid sequences; and a measuring method for 8-OHdG in a specimen using the antibody or antibody fragment thereof are disclosed.

The complex crystallization method is adopted, rapid separation of guanosine impurities can be achieved, the purity of deoxyguanosine reaches 98% or above, and the method is simple, convenient and easy to operate and quite suitable for industrial production.

Compositions and methods relating to a pharmacological therapy for a human genetic disease, specifically mitochondrial DNA depletion-deletions syndromes, and more specifically, those related to mutations in the GUK1 gene. The pharmacological therapy involves the administration of deoxyguanosine (dG), a purine nucleoside phosphorylase (PNP) inhibitor, including but not limited to forodesine, or both.

The application discloses an application of a small-molecule compound in preventing and treating plant RNA virus infection and belongs to the technical field of biotechnology. 2'-amino-2'-deoxyguanosine (ADG) is applied as the only antiviral active ingredient in plant RNA virus prevention for the first time, only a low concentration of 250 muM is needed, and a simple exogenous spraying method can achieve the broad-spectrum inhibition of various plant RNA viruses such as turnip mosaic virus (TuMV), tomato mosaic virus (ToMV) and tobacco mosaic virus (TMV), and after spraying, the normal growth of plants is not affected, the risk of drug damage is completely avoided, the safety, high efficiency and broad spectrum of plant RNA virus prevention are significantly improved, and the application has important practical application significance for guaranteeing the yield and quality of crops in agricultural production and promoting the green transformation of agriculture.