40 results about "Thymidine" patented technology

The invention discloses a Cb Ago-based TdT detection reagent and a Cb Ago-based TdT detection method. The TdT detection reagent comprises a TdT extension reaction system and a TdT detection system, wherein the TdT extension reaction system comprises a TdT reaction buffer solution, deoxythymidine triphosphate, cobalt ions and an extension reaction detection probe; the Cb Ago system comprises Cb Ago, a Cb Ago buffer solution and a fluorescence report probe. The extension reaction detection probe disclosed by the invention can extend under the action of TdT, and then is in specific complementary pairing with the fluorescent reporter probe to activate Cb Ago to cut the fluorescent reporter probe, so that TdT detection is realized. The high specificity of the TdT extension reaction and the signal amplification capacity of Cb Ago are combined, and the method has the advantages of being easy and convenient to operate, high in sensitivity, low in cost, suitable for on-site detection and the like and is expected to become a powerful tool for detecting TdT.

There is provided a method for diagnosing a subject with early onset muscle atrophy, said method comprising: obtaining a biosample from the subject; and assaying the biosample for one or more biomarkers, said one more biomarkers are taurine, proline, citrulline, trigonelline, thymidine, ornithine, glutamate, L-pyroglutamic acid, creatinine, adenine, nicotinamide, 2-methylhippuric acid, maltol, L-arginine, hypotaurine, L-glutamine, homogentisic acid, methylhistidine, oxoglutaric acid, xanthine, L-carnitine, succinate, or a combination thereof; and identifying the subject with early onset muscle atrophy on the basis of a deviation in the one or more of said one more biomarkers.

This invention discloses a trimethyl chitosan-hyaluronic acid-FMNL2 siRNA nanomedicine and its applications. The siRNA molecule consists of a sense strand and an antisense strand, which are anti-complementary to form a double-stranded RNA structure. Each of the sense and antisense strands independently contains two pendant deoxythymidines at its 3' end. The nanomedicine uses trimethyl chitosan as its core framework, efficiently encapsulating the siRNA molecule through electrostatic interactions, and then modifying hyaluronic acid through electrostatic interactions to form core-shell structured nanoparticles. This invention forms a complete technology chain from target validation, siRNA sequence design, nanodelivery system construction, in vivo and in vitro efficacy verification to the development of combination drug strategies. It also provides quantifiable efficacy evaluation biomarkers, offering a clear basis for clinical patient screening and efficacy monitoring.

Provided herein are methods of treating a cancer, comprising administering to a patient diagnosed with cancer an effective amount of a thymidine analog and a thymidylate synthase inhibitor, wherein the thymidine analog incorporates into DNA.

This disclosure relates to the modified 3' region elements that confer improved therapeutic properties including, but not limited to, increased stability, increased expression, and / or a reduced innate immune response when introduced into a population of cells, even in the absence of a 5'-cap. The disclosure also provides polynucleotides (e.g., RNA molecules) containing modified 3' regions. In some embodiments of the disclosure, the modified 3' regions contain modified adenosines (e.g., 2'-0-methoxy- adenosine, 2'-fluoro-adenosine, or locked nucleic acid (LNA)-adenosine) and / or a modified thymidine (e.g., inverted deoxythymidine). In some embodiments of the disclosure, the modified 3' region may contain one or more modified internucleoside linkages (e.g., a phosphorothioate linkage) or modified nucleobase (e.g., N1-methyl-pseudouridine). The polynucleotides of the disclosure may be used to express a desired polypeptide in a subject, such as a subject having a disease or condition associated with a deficiency in the corresponding endogenous polypeptide.

The application provides an immune cell culture kit, a culture method and application of gamma delta T cells, and the kit comprises a basic culture medium, a recombinant antibody, a cytokine and a cell proliferation promoting additive, the basic culture medium comprises an RPMI-1640 culture medium, and the cell proliferation promoting additive comprises 1-thioglycerol, taurine, beta-cyclodextrin, thymidine, alpha-lipoic acid, beta-mercaptoethanol and bisphosphonate. The gamma delta T cells obtained by the culture kit have high purity and activity, and have good tumor killing activity. The gamma delta T cells obtained by the method have a high positive rate of 100% of perforin expression.

The application discloses a HAT probe with adjustable switch characteristics and application thereof, which comprises a secondary structure capable of forming specific steric hindrance, the secondary structure is a convex "bubble" or "ring", and the core of the secondary structure is a polydeoxythymidine sequence with a length of 5-30 nucleotides. The HAT probe has a "switch" regulation function: a molecular switch is constructed by utilizing the inhibition and activation of Cas12a activity of the complete structure and the linear structure after cutting of the HAT probe. The "switch" can respond to specific biomolecules (such as miRNA, protein), and convert the existence of the biomolecules into a detectable signal.

Methods and formulations are provided for treating cancer and neoplastic diseases in conjunction with radiation therapy where such methods and formulations include a combination of a radiosensitizing agent that is metabolized by thymidine phosphorylase and a thymidine phosphorylase inhibitor that increases the half-life of the radiosensitizing agent.

The invention relates to high-purity thymine, a process of purification of thymine, a process for preparing high-purity deoxythymidine, pharmaceutical compositions containing high-purity deoxythymidine and deoxycytidine as well as their use as pharmaceuticals for treatment of mitochondrial depletion syndromes in a mammal.

The invention discloses thymine-containing polyolefin as well as a preparation method and application thereof, the structural formula of the polyolefin is shown in the specification, x is equal to 100-400, and R is phenyl. Norbornene monomer NBT containing nuclear basic groups is synthesized and is copolymerized with cyclooctene (COE) through ring-opening metathesis polymerization (ROMP), and long-chain alkane is introduced to improve the toughness of the polymer; and a series of polymers with ultra-high molecular weight are synthesized by changing the proportion. The NBT in the polymer enables the polymer to have good hydrophobic performance, and the NBT as a hot melt adhesive has good adhesion performance to different substrates.

The invention provides a culture medium suitable for fermentation of Ralstonia solanacearum bacteriophage, a culture method and application. The culture medium comprises thymidine and L-tryptophan. The culture medium provided by the invention can realize more effective culture and fermentation of Ralstonia solanacearum bacteriophage, improves the titer of bacteriophage fermentation liquor in a tank, and has the advantages of simple preparation method, more scientific components and suitability for industrial production.

The invention relates generally to a pharmacological therapy for human genetic diseases, specifically those characterized by unbalance nucleotide pools, more specifically mitochondrial DNA depletion syndromes, and more specifically, thymidine kinase 2 (TK2) deficiency. The pharmacological therapy involves the administration of at least one deoxynucleoside, or mixtures thereof. For the treatment of TK2 deficiency, the pharmacological therapy involves the administration of either deoxythymidine (dT) or deoxycytidine (dC), or mixtures thereof. This administration of deoxynucleosides is applicable to other disorders of unbalanced nucleotide pools, especially those found in mitochondrial DNA depletion syndrome.

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.

Compounds, compositions, and methods of treatment and prevention of HIV infection are disclosed. The compounds are pyrrolo[2,3-b]pyridines and pyrrolo[2,3-b]pyrimidine JAK inhibitors. Combinations of these JAK inhibitors and additional antiretroviral compounds, such as NRTI, NNRTI, integrase inhibitors, entry inhibitors, protease inhibitors, and the like, are also disclosed. In one embodiment, the combinations include a combination of adenine, cytosine, thymidine, and guanine nucleoside antiviral agents, optionally in further combination with at least one additional antiviral agent that works via a different mechanism than a nucleoside analog. This combination has the potential to eliminate the presence of HIV in an infected patient.

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 invention belongs to the technical field of nucleoside medicine preparation, and particularly discloses a method for efficiently preparing 2-deoxy-D-ribose. According to the method, reactants are added into Escherichia coli fermentation liquor for recombinant expression of thymidine phosphorylase, and acid hydrolysis treatment is carried out after one-step catalytic reaction to directly generate 2-deoxy-D-ribose. The method can be used for catalytically preparing the high-concentration 2-deoxy-D-ribose, so that the production of the 2-deoxy-D-ribose reaches a kilogram level, and large-scale industrialization is realized. The preparation process disclosed by the invention does not need to purify recombinase, is simple, saves cost, saves energy, reduces emission, reduces equipment investment, and further reduces production cost.

The present application provides compositions and methods for preparing and using “heavy” nucleotide derivatives of thymidine or uridine by replacing the oxygen atom attached to one or more of positions with non-radioactive oxygen-18 (18O), administering it to a subject to target a tumor including incorporation into tumor cell DNA, and then treating the tumor with proton beam therapy to transmutate the 18O to 18F, resulting in a break of the new fluorine-phosphorous bond. This chemical event destabilizes ribose-phosphate DNA back-bone and base pairing thus produce single- and double strand breaks, clusters lesions that can lead to irreparable DNA damage and enhanced tumor cell killing. The atomic, chemical, and physical aspects result in the use of lower radiation doses and significantly alter acute and late morbidity of radiotherapy. Heavy thymidine and heavy uridine derivatives labeled with 18O have been made and tested.

The invention relates to C2 '-alkyl substituted nucleoside which comprises at least one of C2'-alkyl substituted thymidine, C2 '-alkyl substituted uridine, C2'-alkyl substituted adenosine and C2 '-alkyl substituted guanosine. The structure of the C2 '-alkyl substituted nucleoside is shown as a formula I or a formula II; the structure of the C2 '-alkyl substituted uridine is shown as a formula III in the specification; the structure of the C2 '-alkyl substituted adenosine is shown as a formula IV; the structure of the C2 '-alkyl substituted guanosine is shown as a formula V. The invention also relates to a preparation method of the C2 '-alkyl substituted nucleoside. According to the C2 '-alkyl substituted nucleoside and the preparation method thereof, the limitation of the prior art on functional group compatibility and operation convenience can be broken through, and the synthesis path of the C2'-alkyl substituted nucleoside can be enriched, so that the research and development process of oligonucleotide drugs is greatly promoted.

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 an aptamer-mediated proximity marker probe, a method and a cell membrane protein interaction analysis method. The proximity marker probe comprises an aptamer targeting a target protein; the tail end of the 5'end of the nucleic acid aptamer is connected with a spacer arm composed of N thymine, the tail end of the spacer arm is modified with alkynyl, the thymine close to the tail end of the spacer arm is modified with biotin, and N is an integer larger than or equal to 2. The method disclosed by the invention has the advantages of high specificity, simplicity in operation, capability of accurately controlling the marking range and the like.

The present disclosure is concerned with altered cytidine deaminases, methods, compositions, and kits for mapping of methylation status of nucleic acids. In one embodiment, altered cytidine deaminases are provided that selectively act on certain modified cytosines of target nucleic acids and converts them to thymidine. Also provided are compositions and kits that include one or more of the proteins and methods for using one or more of the proteins.

The application relates to a TC disease risk prediction modeling method based on a cell proliferation marker, comprising the following steps: collecting sample data; converting a medical imaging examination result into a quantitative TI-RADS classification, and setting a TI-RADS classification of TR-3 and above as an endpoint event; taking multiple physical examination index items with a cell proliferation marker serum thymidine kinase 1 (TK1) detection result as independent variables; and modeling through a regression method, so as to obtain a thyroid cancer (TC) risk prediction model. The application sets the comprehensive classification of the imaging examination result with a determined TC risk as a risk prediction endpoint event, thereby reducing the acquisition cost and difficulty of positive result samples, and making it possible to stably accumulate positive samples. In the same time period, the iteration upgrading feasibility of the risk prediction model obtained by the system is higher.

The application belongs to the technical field of molecular recognition adsorption separation functional material preparation, and discloses a method for preparing a bowl-shaped imprint polymer adsorbent by asymmetric action induced silicon-based imprint droplets and application thereof. The application uses 9-vinyladenine 9-VA as a functional monomer, beta-thymidine as a functional monomer, and forms silicon-based imprint droplets after pre-assembly and hydrolysis of 3-(trimethoxysilyl) methyl propyl methacrylate. Subsequently, ellipsoidal iron oxide particles are synthesized, and the surface of the ellipsoidal iron oxide particles is modified by using PVP as a seed, and the silicon-based imprint droplets are polymerized under the condition of magnetic stirring. Due to the centrifugal force, the mass of the iron oxide particles is much larger than that of the polymer droplets, and the iron oxide particles will drag the polymer droplets to deform and form a larger depression under the action of the asymmetric force. AIBN is added to initiate polymerization and solidification, and the composite bowl-shaped imprint polymer particles containing the iron oxide particles are prepared, which are used for realizing high-selectivity adsorption and separation of dT.

To provide a composition for use in the treatment of mitochondrial DNA depletion and / or multiple deletions syndrome.SOLUTION: Provided is a composition for use in the treatment of mitochondrial DNA depletion and / or deletion syndrome caused by a defect in DNA polymerase gamma subunit 1 (POLG1), the composition comprising more than one canonical deoxyribonucleoside selected from the group consisting of deoxyadenosine, deoxyguanosine, deoxycytidine, and deoxythymidine, wherein the deoxyribonucleosides are present in an equimolar ratio.SELECTED DRAWING: None

The invention relates generally to a method of treatment for a human genetic disease, such as diseases characterized by unbalanced nucleotide pools, e.g., mitochondrial DNA depletion syndromes, and more specifically, thymidine kinase 2 (TK2) deficiency, using gene therapy. The gene therapy may involve administration of one or more constructs, such as a viral vector, containing a nucleic acid encoding a functional protein. The functional protein may correspond to a nuclear gene. For treatment of TK2 deficiency, the gene therapy may involve administration of one or more constructs, such as a viral vector, containing a nucleic acid encoding a functional TK2 enzyme. The treatment may also involve the administration of pharmacological therapy in conjunction with the gene therapy. The treatment protocols of the disclosure, such as those involving gene therapy alone or in combination with pharmacological therapy, can be used to treat, prevent, and / or cure various other disorders of unbalanced nucleoside pools, especially those found in mitochondrial DNA depletion syndrome.

The present invention provides methylcytosine selective deaminases, compositions, kits, and methods of using the thereof, including sequencing methods involving: (a) contacting a DNA substrate comprising cytosine (C) and at least one methylcytosine nucleobase selected from 5-methylcytosine (5mC) and 5-hydroxymethylcytosine, or comprising C and both 5mC and 5hmC, with a methylcytosine selective deaminase to produce a deamination product, wherein the methylcytosine selective deaminase (i) is capable of deaminating 5mC to thymidine (T) and / or deaminating 5hmC to hydroxymethyluridine (hmU), and (ii) preferentially deaminating at least one methylcytosine nucleobase relative to cytosine (C); and (b) sequencing the deamination product, or amplifying the deamination product to produce an amplification product, and sequencing the amplification product to produce a sequence read in each case, wherein the position of C and the position of at least one methylcytosine nucleobase in the DNA substrate are determined based on the sequence read.

The thymidine phosphorylase progenitor enzyme is provided on the basis of a strategy of combining progenitor enzyme reconstruction and catalytic efficiency prediction, and compared with a wild type, the thermal stability and catalytic activity of the thymidine phosphorylase progenitor enzyme are remarkably improved. The thymidine phosphorylase ancestor enzyme and purine nucleoside phosphorylase can be synthesized into 2 ' / 3'-modified purine nucleoside through a cascade transglycosylation reaction, and the thymidine phosphorylase ancestor enzyme has important significance in promoting the enzymatic synthesis industrialization process of the 2 ' / 3'-modified purine nucleoside.

The invention relates to an antibiotic composition comprising or consisting of: a purine nucleoside selected from guanosine and xanthosine, or a combination thereof; and an inhibitor of thymidine and / or pyrimidine biosynthesis. A further combination with a Beta-lactam antibiotic can be provided. The invention further relates to associated kits, methods and uses in treatment.

The invention provides a synthesis method of N-protected deoxynucleoside, and belongs to the field of organic synthesis. The invention provides a synthesis method of N-protected deoxynucleoside, which comprises the following steps: mixing beta-thymidine, N-protected basic group, transferase, buffer salt, polar organic solvent and water, and then carrying out condensation reaction on the obtained mixture to obtain the N-protected deoxynucleoside, and the serial number of the transferase is EC 2.4. 2.6. According to the synthesis method, basic group thymine is removed from beta-thymidine under the catalysis of the transferase with the serial number of EC 2.4. 2.6, then the beta-thymidine reacts with N-protected basic groups under the action of the transferase to generate N-protected deoxynucleoside, compared with a traditional process, two-step reaction is reduced, the synthesis method is simple in process, disubstituted by-products are eliminated, the variety of impurities is reduced, and the synthesis method is suitable for industrial production. The method is suitable for large-scale production of nucleic acid drug intermediates.

The invention discloses a capture probe composition, a kit and application. The composition comprises a membrane binding molecule, polydeoxythymidine, a connecting arm and a probe s1 which is formed by sequentially connecting an initiation nucleic acid fragment 1 with the sequence shown as SEQ ID NO: 1, the probe s2 is formed by sequentially connecting an initiation nucleic acid fragment 2 of which the sequence is shown as SEQ ID NO: 2, a connecting arm, polydeoxythymidine and a membrane binding molecule; the probe H contains nucleic acid fragments for triggering complementary pairing of a nucleic acid fragment 1 and a nucleic acid fragment 2, and can spontaneously form a hairpin-shaped structure; the solid-phase carrier is used for loading nucleic acid fragments which can be complementarily paired with the connecting arms of the probes s1 and s2 on the basis of a Hoogsteen principle. The composition can be specifically combined with extracellular vesicles to realize specific separation and purification; the operation is simple, convenient, rapid and soft, and the potential damage to extracellular vesicles is small; the magnetic beads are used as solid-phase carriers and can be repeatedly used for more than five times, so that the capturing efficiency is relatively high, the economical efficiency is good, and the potential of large-scale application is realized.