52 results about "Deoxyadenosine" patented technology

The invention relates to a saccharomyces cerevisiae strain for efficiently synthesizing cordycepin as well as a construction method and application of the saccharomyces cerevisiae strain, and belongs to the technical field of microbial genetic engineering. The construction method provided by the invention comprises the following steps: carrying out multi-copy genome integrated expression on heterologous codon optimized 2 '-carbonyl-3'-deoxyadenosine reductase genes and 3 '-adenosine monophosphate phosphohydrolase genes, so as to increase the dosage of key enzymes; and supplementing the defective gene of the engineering strain to obtain the saccharomyces cerevisiae strain B5U3 with high yield of cordycepin. According to the obtained saccharomyces cerevisiae strain for efficiently synthesizing the cordycepin, the cordycepin yield reaches 2.92 g / L after shake flask fermentation, the cordycepin yield reaches 7.5 g / L after fermentation in a fermentation tank, and a foundation is laid for safer and more reliable industrial production of the cordycepin.

The invention relates to the technical field of microbial genetic engineering, in particular to a method for improving cordycepin synthesized by saccharomyces cerevisiae and saccharomyces cerevisiae engineering bacteria. According to the invention, codon-optimized 2 '-carbonyl-3'-deoxyadenosine reductase gene and 3 '-adenosine monophosphate phosphohydrolase gene from cordyceps militaris are expressed by using plasmids, and then the plasmids are transformed into host cells to obtain the saccharomyces cerevisiae engineering bacteria. And inoculating a seed solution obtained by seed culture of the activated saccharomyces cerevisiae engineering bacteria into a fermentation culture medium containing a metabolic effector, and carrying out fermentation culture to synthesize cordycepin. Metabolic effectors (Cu < 2 + >, Fe < 2 + >, Mg < 2 + >, Zn < 2 + >, citric acid, cysteine, aspartic acid, glycine, VB1 and tea polyphenol) are added into a fermentation culture medium strain, and the variety and concentration of the metabolic effectors are optimized, so that the yield and synthesis efficiency of cordycepin are remarkably improved. By using the combination of the strain obtained by the invention and the optimal effector, the yield of cordycepin in a fermentation tank reaches 2.9 g / L.

The invention provides a hydrogel dressing for synergistically promoting chronic wound healing through near-infrared controlled release of ROS (reactive oxygen species) and NO (nitric oxide) as well as a preparation method and application of the hydrogel dressing. Belongs to the technical field of biomedical materials. The hydrogel is prepared from the following components: upconversion nanoparticles as a core, silicon dioxide wrapping, carbon dot and L-arginine loading, maltotriose modification, and mixing and gelling with 2-amino-2-fluoro-2-deoxyadenosine as a hydrogel carrier, so as to obtain the hydrogel dressing. The obtained hydrogel dressing has the functions of inhibiting bacteria, promoting cell proliferation, promoting revascularization and the like, and remarkably promotes skin wound healing.

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 present invention belongs to the technical field of microbial genetic engineering, and particularly relates to an engineered strain for producing 2'-deoxyadenosine, a preparation method thereof and an application thereof. The engineered strain expresses a ketodeoxyadenosine reductase gene cns1 and an adenylic acid dephosphatase gene cns2 . The engineered strain prepared by the preparation method of the present invention has obvious advantages in the production of 2'-deoxyadenosine. By optimizing the fermentation medium conditions, the present invention improves the yield and efficiency of Corynebacterium glutamicum in synthesizing 2'-deoxyadenosine to varying degrees, and the yield reaches 702.3 mg / L on a 6L bioreactor.

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.

The present invention provides a 5'-methylthioadenosine phosphorylase mutant, the amino acid sequence of which is derived from a mutation of the sequence shown in SEQ ID No. 3 of the sequence table, wherein the mutation is selected from at least one of the following: H64A, P131D, W114N, L206S, E168Q, F217V, F217S, F217W, R219A, R219Q, R219F, V184A and V184T. The present invention also provides its application in the catalytic synthesis of 2'-fluoro-2'-deoxyadenosine. The mutant H64A / W114N / L206S of the present invention has an enzyme activity of 1.31 U / g, while the ApMTAP unmutated enzyme strain has an enzyme activity of 0.11 U / g, which is about 12 times higher than the enzyme activity, that is, the yield of 2'-fluoro-2'-deoxyadenosine has been greatly improved, and is suitable for the field of enzyme catalysis.

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

The invention belongs to the technical field of gene engineering, and provides a method for improving cordycepin synthesized by a strain through lipid droplet engineering modification and application. Based on the characteristic that key enzymes (ketodeoxyadenosine reductase and adenylate dephosphatase) synthesized by cordycepin are positioned on lipid droplets, the synthesis efficiency of the product is improved by increasing the number or volume of the lipid droplets. The lipid droplet engineering modification comprises the following steps: intensively expressing a dga1 gene, an lro1 gene, a pah1 gene or an acc1 gene; the hrd1 gene, the erde1 gene, the opi3 gene or the fld1 gene are inactivated / weakened; cu < 2 + > is exogenously added into the culture medium. Wherein the hrd1 and the erdes 1 are inactivated / weakened at the same time, so that the number of lipid droplets can be increased synergistically, and the yield of cordycepin is increased by 37.7%. The production efficiency of cordycepin is remarkably improved through targeted lipid droplet regulation and control, and the method has the potential of industrial application.

The present invention discloses a capillary monolithic column modified with a deoxyribozyme nanoflower, a preparation method thereof, and an application thereof in separating chiral molecules, belonging to the field of pharmaceutical analysis. The present invention synthesizes a deoxyribozyme-based nanoflower chiral selector, the nucleotide sequence of the single-stranded DNA template of the deoxyribozyme being shown in SEQ ID NO.1, and the synthesized deoxyribozyme nanoflower having good pH and temperature stability. The prepared deoxyribozyme nanoflower is bonded to a graphene oxide-functionalized capillary silica monolithic column, and chiral molecules are separated under electrophoretic conditions, achieving baseline separation of 2'-deoxyadenosine, atenolol, propranolol, tyrosine, and nafopam enantiomers.

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 provides a ketodeoxyadenosine reductase mutant and application thereof in biosynthesis of cordycepin. The invention relates to a method for improving the yield of cordycepin by constructing the ketodeoxyadenosine reductase mutant. The method comprises the following steps: mutating ketodeoxyadenosine reductase, and screening to obtain a mutant containing any one or a combination of more of key amino acid site mutations such as N19S, A31T, L124P, Y256F, V387I, G406A, A485V and V666A. The invention also provides a high-throughput screening method of the mutant, an expression vector and a host cell comprising the nucleotide, and a fermentation process for producing cordycepin by using the mutant. When the ketodeoxyadenosine reductase mutant disclosed by the invention is expressed in saccharomyces cerevisiae, the yield of cordycepin is increased by 6%-36.8%.

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.

The invention discloses a gene engineering strain with high yield of 3 '-deoxyadenosine and application of the gene engineering strain, and belongs to the technical field of gene engineering. The genetic engineering strain is obtained by carrying out genetic modification on the strain, and the genetic modification comprises at least one of the following steps: a) overexpressing a ribonucleotide reductase gene rnr1; b) inactivating / weakening an adenosine kinase gene ad1; c) inactivating / weakening the adenine deaminase gene aah1; d) overexpressing a ribonuclease gene rny1; and e) an inactivation / weakening inhibition type vacuolar alkaline phosphatase gene pho8. According to the method, substrate metabolism kinetics is accurately matched in combination with an intermittent feeding strategy, finally, the yield of 3 '-deoxyadenosine reaches 20.58 g / L and reaches the highest yield reported at present, a'gene-process' dual-drive technical barrier is formed, and an efficient, stable and low-cost solution is provided for industrial production of nucleoside compounds.

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 present disclosure relates to systems, methods and compositions for nucleic acid modification (e.g., base editing) by using a nucleic acid deaminase or a base editor comprising the nucleic acid deaminase. The nucleic acid deaminase is capable of deaminating a deoxyadenosine (dA) in a nucleic acid molecule and comprises an amino acid sequence of a wild-type TadA, wherein one or more amino acid residue(s) of the wild- type TadA are deleted and wherein the one or more deleted amino acid residue(s) are located within a region of the wild-type TadA contacting the nucleic acid molecule.

The present invention relates to chemical compounds, the compounds for use in a method of treatment, particularly in a method of prophylaxis or treatment for cancer, a process for preparation of the compounds and pharmaceutical compositions comprising the compounds. The compounds may, in particular, be useful in the treatment of leukaemia, lymphoma and / or solid tumours in Homo sapiens. The compounds are derivatives of cordycepin (3′-deoxyadenosine).

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.

The invention discloses a plasma metabolism composition for predicting atrial fibrillation related cerebral apoplexy and application of the plasma metabolism composition. The plasma metabolism composition is prepared from a plasma metabolite, namely 7-hydroxy-6-methoxy-2H-chromene-2-ketone, deoxyadenosine, arachidonic acid, choline glycerophosphate, eicosapentaenoic acid, fumaric acid and thromboxane B3. The invention further discloses a preparation method of the plasma metabolism composition. The seven screened metabolites are more intuitive, so that researchers can analyze the key metabolites more intensively. The method has the advantages that the detection time is effectively saved, the detection efficiency is improved, the detection cost is reduced, the plasma metabolism composition prediction method based on the molecular level is remarkably different from a traditional clinical complication scoring strategy-based prediction mode, the prediction accuracy is higher, and the method is suitable for popularization and application. And a new technical means is provided for solving the problem of predicting the cerebral apoplexy related to the atrial fibrillation.

The present invention relates to the use of 2-chloro-2′-deoxyadenosine, hereinafter referred to as cladribine, or a pharmaceutically acceptable salt thereof, for treating or ameliorating an autoimmune, neuromuscular disorder, e.g. the autoimmune neuromuscular disorder myasthenia gravis (MG).

To provide antiviral prodrugs and formulations thereof.SOLUTION: The disclosure provides compounds, compositions and use methods thereof for treating and / or preventing viral infections such as HIV and HBV by administering a specific ester and other derivatives or pharmaceutically acceptable salts of 4'-ethynyl-2-fluoro-2'-deoxyadenosine (EFdA).SELECTED DRAWING: None

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 application provides a nucleoside supramolecular hydrogel and a preparation method and application thereof, and belongs to the field of biological materials. The nucleoside supramolecular hydrogel is prepared from 2,2'-diamino-2'-deoxyadenosine and cyanuric acid as raw materials. The nucleoside supramolecular hydrogel has good stability, can effectively promote alveolar bone defect bone repair and periodontitis bone defect repair, and has a wide application prospect in the preparation of bone defect repair materials.

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.