24 results about "Deoxyadenosine" patented technology

Diesters of 4'-ethynyl-2-fluoro-2'-deoxyadenosine and aqueous parenteral suspensions thereof provide extended in vivo viral suppression of human immunodeficiency virus (HIV).

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.

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 belongs to the technical field of preparation of molecular identification, adsorption and separation functional materials, and discloses a preparation method and separation application of a surface post-crosslinked molecularly imprinted polymer. According to the invention, an adhesion strategy and a surface post-crosslinking imprinting technology are combined to realize rapid and specific separation of 2 '-deoxyadenosine dA, and finally, a novel synthesis scheme related to preparation of functional copolymer modified wrinkle structure nano-silica WSNs is used to construct a surface post-crosslinking imprinting polymer WSNs (at) SPMIPs on WSNs. The method comprises the following steps: firstly, preparing WSNs of radial branches through a progressive seed growth mechanism; secondly, synthesizing a functional copolymer CP through free radical copolymerization; and then, pre-assembling the template molecule dA and the affinity monomer group in the CP, carrying out irradiation induction under ultraviolet light, carrying out post-crosslinking polymerization, and eluting the template to obtain the post-crosslinking imprinted polymer PMIPs. DA (Dopamine) is deposited on the WSNs under the mediation of DMSO (Dimethylsulfoxide); and finally, PMIPs are grafted on the surfaces of the WSNs, so that the adsorbent WSNs (at) SPMIPs is finally prepared and is used for the adsorption separation research of dA.

The application discloses a 3'-deoxyadenosine compound and application thereof in preparation of an antitumor drug. The 3'-deoxyadenosine compound and the pharmaceutical composition thereof have good antitumor proliferation effect. Compared with a parent drug, the 3'-deoxyadenosine compound has better affinity to a cell membrane, so that the half-life of in-vivo metabolism of the drug is longer, and the drug stays in the body for a longer time. Compared with other nucleoside antitumor drugs, the cordycepin derivative and the pharmaceutical composition thereof have a wider range of tumor types and effects, including excellent inhibition effect on gastric cancer, pancreatic cancer, liver cancer, small cell lung cancer, colorectal cancer, melanoma, ovarian cancer and the like, and the side effect is lower and the curative effect is better.

Diesters of 4′-ethynyl-2-fluoro-2′-deoxyadenosine and aqueous parenteral suspensions thereof provide extended in vivo viral suppression of human immunodeficiency virus (HIV).

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.

The application discloses a compound with anticancer effect based on 3'-deoxyadenosine modified by chemical modification, and a structure of the compound is shown as formula I. The cordycepin derivative and the pharmaceutical composition thereof have good antitumor proliferation effect. Compared with the parent drug, the cordycepin derivative has better affinity to the cell membrane, so that the half-life of the drug metabolism in the body is longer, and the drug stays in the body for a longer time. Compared with other nucleoside antitumor drugs, the cordycepin derivative and the pharmaceutical composition thereof have a wider range of tumor types and effects, including excellent inhibition effect on gastric cancer, pancreatic cancer, liver cancer, small cell lung cancer, colorectal cancer, melanoma, ovarian cancer and the like, and the side effect is lower and the curative effect is better.

To provide methods for treating diseases.SOLUTION: The present disclosure provides prodrugs of 4'-C-substituted-2-halo-2'-deoxyadenosine nucleosides, and compositions, methods and kits thereof. Such compounds can be useful for treating virus infections including human immunodeficiency virus. The compounds have the following formula (I). Provided herein are compounds functioning as antiviral agents (in some embodiments, as anti-HIV agents), pharmaceutical compositions comprising such a compound and optionally in combination with one or more (e.g., two, three or four) additional therapeutic agents, and methods for using such compounds and compositions. Embodiment of every disclosed compound includes pharmaceutically acceptable salts and stereoisomers thereof or a mixture of the stereoisomers.SELECTED DRAWING: None

This invention provides a nucleic acid aptamer that targets and binds to the IGF2BP2 protein and its application, belonging to the field of pharmaceutical technology. This invention is the first to design a highly specific nucleic acid aptamer targeting the RNA recognition protein IGF2BP2, obtaining a nucleic acid aptamer that can target and specifically bind to the IGF2BP2 protein (see SEQ ID No. 1-2). This nucleic acid aptamer can effectively inhibit the activity of tumor cells, tumor stem cells, and breast cancer brain metastases, breast cancer lung metastases, breast cancer liver metastases, breast cancer kidney metastases, and breast cancer bone metastases, providing a new drug component for the treatment of malignant and refractory tumors (especially glioblastoma and distant metastatic breast cancer). Furthermore, it was discovered that modification with N6-methyldeoxyadenosine monophosphate can further enhance the specificity of the nucleic acid aptamer and strengthen its efficacy in inhibiting tumor cell activity.

The present disclosure provides prodrugs of 4'-C-substituted-2-halo-2'-deoxyadenosine nucleosides and compositions, methods, and kits thereof. Such compounds are useful for treating viral infections, including human immunodeficiency virus. These compounds have the following formula (I).

The application provides a nucleic acid aptamer for treating malignant tumors and application thereof, and relates to the technical field of medicines. In the application, a nucleic acid aptamer with high specificity is designed for the RNA recognition protein YTHDF2 for the first time, and the nucleic acid aptamer is screened, and a DNA nucleic acid aptamer capable of targeting the YTHDF2 protein and specifically combining with the YTHDF2 protein is obtained, the nucleic acid aptamer can effectively inhibit the activity of malignant tumors, including glioblastoma, lung cancer, liver cancer, esophageal cancer and the like, and provides a new drug component for the treatment of malignant tumors. N 6-methyl deoxyadenosine acid modification, it is found that after modification, the specificity of the nucleic acid aptamer targeting YTHDF2 and the efficacy of selectively inhibiting the activity of tumor cells can be further improved.

The invention relates to a high-performance RNA (Ribonucleic Acid) off-target detection report system as well as a construction method and application thereof. According to the invention, several modules of an MS2-MCP system, deoxyadenosine deaminase, mCherry and BFP are fused, and a fluorescence report system for indirectly detecting the miss of deoxyadenosine deaminase RNA through fluorescence and a sequencing report system for directly detecting the miss of deoxyadenosine deaminase RNA through sequencing are developed. The RNA off-target detection report system comprises an RNA off-target fluorescence report system and an RNA off-target sequencing report system. The RNA off-target detection report system can be effectively applied to RNA off-target risk assessment of the ABE base editing tool. The RNA off-target detection report system obtained through the method is convenient to operate, short in period, low in cost and high in sensitivity, effectively makes up for the shortages of RNA off-target detection in the current base editing field, and has very wide application prospects.

The application relates to the technical field of biological medicines, in particular to a purification method of 2'-fluoro-2'-deoxyadenosine; the purification method of 2'-fluoro-2'-deoxyadenosine comprises the following steps: (1) crude 2'-fluoro-2'-deoxyadenosine containing adenine shown in formula I is reacted with an acetylation reagent under alkaline conditions, and after purification, diacetylated 2'-fluoro-2'-deoxyadenosine shown in formula II is obtained, and adenine is removed; (2) diacetylated 2'-fluoro-2'-deoxyadenosine shown in formula II is deacetylated under the action of ammonia to obtain crude product shown in formula III, and then beating is carried out to obtain 2'-fluoro-2'-deoxyadenosine pure product; the application solves the purification problem of crude 2'-fluoro-2'-deoxyadenosine obtained by an enzyme method, uses cheap and easily obtained raw materials and simple chemical reactions, and provides a method for avoiding column chromatography operation to remove adenine, and the method is easy to scale up.

The application discloses application of a halogenase in catalyzing synthesis of 2'-halogenated nucleosides. The halogenase is any one of NSH1, NSH2, NSH3, NSH4 and NSH5, and the substrate used in the catalysis is any one of 2'-deoxyguanosine, 2'-deoxyinosine and 2'-deoxyadenosine. The biosynthesis method has the advantages of high stereoselectivity, high product yield, simple halogen source, easy control of operation process, low production cost, green and environmentally-friendly reaction and high catalytic activity, and provides a new method for synthesis of 2'-halogenated compounds.

This invention relates to the field of enzyme engineering, and discloses a mutant enzyme with halogenation activity, its enzyme preparation, encoding gene, recombinant vector, recombinant strain, and applications. The mutant enzyme is an S-adenosyl-L-methionine hydrolase with an amino acid sequence as shown in SEQ ID NO.1, comprising at least one mutation at the F19, P83, and R89 sites; wherein the mutation at the F19 site is selected from at least one of F19P, F19C, and F19L; the mutation at the P83 site is selected from at least one of P83F, P83H, P83E, P83D, P83C, P83L, P83K, and P83I; and the mutation at the R89 site is selected from at least one of R89A, R89C, R89E, R89F, R89S, R89T, R89Q, R89H, and R89D. All of the above mutations enable the enzyme to acquire the new function of catalyzing the production of 5'-halodeoxyadenosine from S-adenosine-L-methionine, exhibiting excellent iodination catalytic efficiency. Its activity exceeds that of wild-type enzymes and is superior to known natural halogenases, thus solving the technical problems of scarce natural halogenase resources and severe chemical halogenation pollution.

4'-ethynyl-2-fluoro-2'-deoxyadenosine diesters and aqueous parenteral suspensions thereof provide extended in vivo viral suppression of the human immunodeficiency virus (HIV).

The present disclosure provides prodrugs of 4'-C-substituted-2-halo-2'-deoxyadenosine nucleosides and compositions, methods, and kits thereof. Such compounds are useful for treating viral infections, including human immunodeficiency virus. These compounds have the following formula (I).

The invention belongs to the field of medicine and cosmetics, and particularly relates to a tetrahydromethylpyrimidine carboxylic acid composition, a nasal medicine preparation and a preparation method of the nasal medicine preparation, the composition comprises tetrahydromethylpyrimidine carboxylic acid and 2-amino-2 '-fluoro-2'-deoxyadenosine, and the nasal medicine preparation comprises the tetrahydromethylpyrimidine carboxylic acid composition and a buffer solution, the mass concentration of the 2-amino-2 '-fluoro-2'-deoxyadenosine is 1.6-2.2%, and the preparation method comprises the following steps: firstly preparing a tetrahydromethylpyrimidine carboxylic acid solution, then preparing a 2-amino-2 '-fluoro-2'-deoxyadenosine solution, heating, then mixing with the tetrahydromethylpyrimidine carboxylic acid solution, and heating and cooling to room temperature. The traditional Chinese medicine preparation is comfortable to use, mild and non-irritating, can prevent impurities from entering the body, also has the effects of inhibiting bacteria, resisting inflammation and repairing damaged nasal mucosa, and particularly, the medicine preparation stays in the nasal cavity for a long time, so that the medicine can fully play a role.

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 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 discloses a high-efficiency fluorinase mutant and application thereof in synthesis of 5 '-fluoro-5'-deoxyadenosine, and belongs to the technical field of bioengineering and enzyme engineering. According to the mutant, on the basis of an amino acid sequence (SEQ ID NO: 1) of wild type MA37, at least one mutation selected from the following groups is introduced: in an N-terminal hydrophobicity enhancing sequence, alanine at the 264th site of a core region is mutated into valine (A264V), arginine at the 92nd site of a far end is mutated into glycine (R92G), or arginine at the 92nd site is mutated into asparagine (R92N). According to the method, the reaction efficiency is remarkably improved, the overall structural rigidity of the mutant is enhanced through N-end-far-end-core region collaborative transformation, and the method is more suitable for industrial application.

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 present application relates to the technical field of gene editing, and relates to a base editor and a construction method and application thereof.The present application fuses cytidine deaminase and its mutant to different sites of mutant nucleases represented by Cas12f1 to obtain new fusion proteins which can realize effective C-T base mutation of cytosine located at different positions of a protospacer sequence, fuses deoxyadenosine deaminase and its mutant to different sites of mutant nucleases represented by Cas12f1 to obtain new fusion proteins which can realize effective A-G and / or C-T base mutation of adenine and / or cytosine located at different positions of a protospacer sequence.The different insertion site-based fusion proteins obtained by the method of the present application have different mutation ranges.The base editor of the present application has a smaller size and a diversified activity window, can realize wider, more precise and safer C-T single base substitution and A-G single base substitution, and can effectively widen the application of single base editing tools.