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45 results about "Ribonucleotide reductase" patented technology

Ribonucleotide reductase (RNR), also known as ribonucleotide diphosphate reductase (rNDP), is an enzyme that catalyzes the formation of deoxyribonucleotides from ribonucleotides. It catalyzes this formation by removing the 2'-hydroxyl group of the ribose ring of nucleoside diphosphates. This reduction produces deoxyribonucleotides. Deoxyribonucleotides in turn are used in the synthesis of DNA. The reaction catalyzed by RNR is strictly conserved in all living organisms. Furthermore, RNR plays a critical role in regulating the total rate of DNA synthesis so that DNA to cell mass is maintained at a constant ratio during cell division and DNA repair. A somewhat unusual feature of the RNR enzyme is that it catalyzes a reaction that proceeds via a free radical mechanism of action. The substrates for RNR are ADP, GDP, CDP and UDP. dTDP (deoxythymidine diphosphate) is synthesized by another enzyme (thymidylate kinase) from dTMP (deoxythymidine monophosphate).

In vivo measurement of the relative fluxes through ribonucleotide reductase vs. deoxyribonucleoside pathways using isotopes

InactiveUS20050255509A1Increase salvageHigh activityCompound screeningApoptosis detectionRate-determining stepDeoxyribonucleotide biosynthesis
The methods of the present invention allow for the measurement of ribonucleotide reductase (RR) activity, an important enzyme in the de novo DNA synthesis pathway. Ribonucleotide reductase converts all four ribonucleotides to their deoxy form and is a rate-controlling step in this pathway. Biosynthetic pathways of deoxyribonucleotides (dN) have received considerable attention in the context of anti-proliferative chemotherapy. Inhibitors of various steps in dN biosynthesis, including inhibitors of RR are among the most useful chemotherapeutic agents in cancer, viral infections, and other therapeutic uses. DNA synthesis from the dN salvage pathway is also an important component to DNA replication. The relative contributions from RR vs. salvage pathways are critical to the actions and effectiveness of chemotherapeutic agents that act on nucleoside metabolic pathways. Until now, however, it has not been possible to study these metabolic processes in vivo. Disclosed within are methods of measuring RR activity in vivo and in vitro which find use, among other things, in drug discovery, development, and approval.
Owner:KINEMED

Vectors, cells and processes for pyrimidine deoxyribonucleosides production

Novel DNA constructs and host cells comprising the same are disclosed. DNA constructs comprise a transcription unit (e.g. operon) comprising DNA sequences encoding for ribonucleotide reductase and thioredoxin. In preferred embodiments, constructs further comprise DNA sequences encoding for thymidylate synthase and / or transcription units comprising sequences encoding for uridine kinase preferably together with dCTP deaminase. In particularly preferred embodiments, host cells comprising constructs having all of the above characteristics wherein the host cell displays repressed or no uracil DNA glycosylase activity. This may be achieved by removal of the host cell ung gene. Use of host cells in the manufacture of pyrimidine deoxyribonucleotides e.g. thymidine is also disclosed.
Owner:SMITHKLINE BECKMAN CORP

Application of 4-hydroxy salicylamide in preparing medicament for preventing and treating hepatitis and resisting tumor

The invention provides novel application of 4-hydroxy salicylamide in the field of pharmacy. The compound is an inhibitor of ribonucleotide reductase (RR), and can achieve the aims of inhibiting replication of HBV and treating hepatitis, in particular the hepatitis B by inhibiting activity of RR enzyme to block synthesis of dNTPs (deoxynucleotide triphosphates) required by hepatitis B virus (HBV)replication, achieve the aim of preventing and treating liver cancer by inhibiting the activity of RR of liver cancer cells, including the RR activity activated by HBV to inhibit proliferation of liver cancer cells, and achieve the aim of treating various tumors by inhibiting the RR. The 4-hydroxy salicylamide can be used for preventing and treating hepatitis B, liver cancer, oropharyngeal epithelioma, colorectal cancer, ovarian cancer, non-small cell lung cancer, chronic myeloid leukemia and other tumors, and has important application prospect.
Owner:ZHEJIANG UNIV +1

HSV with a Musashi promoter regulating γ34.5 and ribonucleotide reductase expression

The present invention provides a recombinant HSV having the ability to specifically kill tumor cells such as human glioma cells in vivo, useful and safe for treating human glioma, etc. and that can easily put to clinical use. A new recombinant HSV, KeM345, is constructed by inserting a γ34.5 gene transcription unit, which is expressed by Musashi1 promoter, into a ribonucleotide reductase gene site of the genome of a herpes simplex virus (HSV) previously attenuated, by means of homologous recombination and obtained as a purified strain. Since KeM345 is a recombinant virus itself, it can not only induce viral proliferation by being transmitted to culture cells but can also induce viral replication equivalent to that of wild-type HSV, showing an excellent cytotoxic effect (cytolytic ability) selectively upon a malignant glioma.
Owner:KEIO UNIV

Protein capable of promoting chloroplast development and coding gene and application thereof

The invention discloses a rice protein capable of promoting chloroplast development and a coding gene and application thereof. The protein is one of 1) a protein formed by amino acid residue sequences of the SEQ ID No.2 in a sequence table or 2) a protein which is formed after one or more amino acid residues in the amino acid residue sequences of the SEQ ID No.2 in the sequence table are substituted and / or deleted and / or added and has the same activities as the amino acid residue sequences of the SEQ ID No.2. The gene is used for coding the small subunit of ribonucleotide reductase, and the development of rice chloroplast is affected after the gene is mutated so that white stripes are distributed on the rice leaves in the vein direction.
Owner:INST OF GENETICS & DEVELOPMENTAL BIOLOGY CHINESE ACAD OF SCI

Ribonucleoside reductase transcription inhibition factor mutant, mutation gene and application of ribonucleoside reductase transcription inhibition factor mutant and mutation gene to preparation of vitamin B2

The invention discloses a ribonucleoside reductase transcription inhibition factor mutant, a mutation gene and an application of the ribonucleoside reductase transcription inhibition factor mutant andthe mutation gene to preparation of vitamin B2. The amino acid sequence of the mutant is subjected to the following mutation relative to the sequence as shown in SEQID No.3; and an amino acid at the26th site is replaced with H. For the nucleotide fixed point mutation that the amino acid at the 26th site, coded in the ribonucleoside reductase transcription inhibition factor gene on a bacillus subtilis chromosome is replaced with H, a genetic engineering bacterium is obtained, and the capacity for producing the vitamin B2 is greatly improved. The ribonucleoside reductase transcription inhibition factor mutant has great application and extension value.
Owner:TIANJIN INST OF IND BIOTECH CHINESE ACADEMY OF SCI

Bacterial thioredoxin reductase inhibitors and methods for use thereof

The mechanism of action of Ebselen differentiates between bacterial and mammalian thioredoxin reductase (TrxR). It displays fast oxidation of mammalian Trx and via the NADPH-TrxR catalyzed turnover of ebselen selenol with hydrogen peroxide, and therefore are mammalian antioxidants. Ebselen, and its diselenide, are strong competitive inhibitors of E. coli TrxR with Ki of 0.14 μM and 0.46 μM, respectively. E. coli mutants lacking glutathione reductase or glutathione were much more sensitive to inhibition by ebselen. Since either glutaredoxin or thioredoxin systems are electron donors to ribonucleotide reductase, ebselen targets primarily glutathione and glutaredoxin-negative bacteria, a class which includes major pathogens. Ebselen, and similar compounds are therefore useful as antibacterial agents, even for multiresistant strains. Two major pathogenic bacteria, which previously had not been known to be sensitive to ebselen, Mycobacterium tuberculosis (tuberculosis) and Helicobacter pylori (stomach ulcer and cancer), were shown to be excellent targets. Helicobacter pylori was also sensitive to ebsulfur.
Owner:THIOREDOXIN SYST AB

Application of 4-hydroxy salicylanilide to preparation of medicament for preventing and treating hepatitis B

The invention provides new application of 4-hydroxy salicylanilide in the field of pharmacy. 4-hydroxy salicylanilide is an inhibitor of ribonucleotide reductase (RR) and inhibits the enzyme activity of RR, so that the compounding of dNTPs required by reproduction of HBV is blocked, and the aims of inhibiting reproduction of HBV, treating hepatitis and particularly treating hepatitis B are fulfilled. The 4-hydroxy salicylanilide can be used for preventing and treating the hepatitis B and has a significant application prospect.
Owner:ZHEJIANG UNIV +1

Method for detecting exogenous gene copy number in transgenic tobacco

The invention discloses a method for detecting an exogenous gene copy number in transgenic tobacco. A real-time fluorescent quantitation PCR technology is utilized to simply, rapidly and accurately detect the exogenous gene copy number in transgenic tobacco. The invention discloses a pair of primers consisting of DNA molecules shown in (1) and (2), namely (1) a DNA molecule shown in SEQ ID No.3; and (2) a DNA molecule shown in SEQ ID No.4. A single-copy endogenous gene ribonucleotide reductase gene (RNR2) of the tobacco is selected as a reference gene, and the exogenous gene copy number in transgenic tobacco is detected through a SYBR GreenI real-time fluorescent quantitation PCR technology. The method disclosed by the invention provides a new thought for copy number analysis of the transgenic tobacco, and the screening requirement for excellent transformation plants in genetic engineering is met.
Owner:GUANGXI VETERINARY RES INST

Vectors, cells and processes for pyrimidine deoxyribonucleosides production

Novel DNA constructs and host cells comprising the same are disclosed. DNA constructs comprise a transcription unit (e.g. operon) comprising DNA sequences encoding for ribonucleotide reductase and thioredoxin or a uridine kinase gene and / or a dCTP deaminase gene. In preferred embodiments the constructs comprising DNA sequences encoding for ribonucleotide reductase and thioredoxin further comprise DNA sequences encoding for thymidylate synthase and / or transcription units comprising sequences encoding for uridine kinase preferably together with dCTP deaminase. In particularly preferred embodiments, the host cells comprise constructs having all of the above characteristics wherein the host cell displays repressed or no uracil DNA glycosylase activity. This may be achieved by removal of the host cell ung gene. Use of host cells in the manufacture of pyrimidine deoxyribonucleotides e.g. thymidine is also disclosed.
Owner:GLAXO SMITHKLINE LLC

Viral nucleotide sequences

Various genes of herpes virus of turkeys (HVT), Marek's disease virus (MDV) and infectious laryngotracheitis virus (ILTV) have been identified as non-essential regions (and candidates for insertion sites for foreign genes) and / or as antigen-encoding regions. The former include the HVT homologue of the HSV (herpes simplex virus) gC gene, the TX (thymidine kinase) region of MDV or ILTV, ORF3 of ILTV (as defined herein), the ribonucleotide reductase (large subunit) gene of ILTV, MDV or HVT and the ribonucleotide reductase (small subunit) gene of MDV. The antigen-encoding regions include the HVT homologues of the HSV gB, gC and gH genes, the ILTV homologue of HSV gB, ORF2 of ILTV, and the HVT homologue of the HSV-1 immediate early genes IE-175 and IE-68. Manipulation of these genes allows vaccines to be prepared comprising attenuated virus or virus carrying heterologous antigen-encoding sequences.
Owner:MERIAL SAS

Sulfonamide Compound or Salt Thereof

The present invention provides a novel sulfonamide compound having a ribonucleotide reductase inhibitory activity or a salt thereof, and a pharmaceutical composition containing the same as an active ingredient.A compound represented by Formula (I) [wherein, X1 represents an oxygen atom or the like; X2 represents an oxygen atom; X3 represents —NH—; X4 represents a hydrogen atom or the like; R1 represents —C(R11)(R12)— or the like; R11 and R12 are the same or different and each represents a hydrogen atom or the like; R2 represents an optionally substituted C6-C14 aromatic hydrocarbon group or the like; R3 represents an optionally substituted C6-C14 aromatic hydrocarbon group or the like; R4 represents a hydrogen atom or the like] or a salt thereof.
Owner:TAIHO PHARMA CO LTD

Application of RRM2B gene or protein thereof in metastasis of hepatocellular carcinoma

The invention discloses application of RRM2B gene or protein thereof in metastasis of hepatocellular carcinoma, and particularly provides application of detection reagents of ribonucleoside-diphosphate reductase subunit M2B (RRM2B) gene or protein thereof, as well as the RRM2B gene or protein thereof for preparing kits for diagnosing metastasis of hepatocellular carcinoma. Furthermore, the RRM2B has an inhibiting effect on metastasis of hepatocellular carcinoma, and a new approach is provided to diagnosis and treatment of metastasis of hepatocellular carcinoma.
Owner:SHANGHAI INST OF ONCOLOGY

Method, kit, primer and probe for detecting relative expression quantity of RRM1 (ribonucleotide reductase M1) mRNA (messenger ribonucleic acid)

The invention provides a method for quantitatively detecting the relative expression quantity of RRM1 (ribonucleotide reductase M1) mRNA (messenger ribonucleic acid) in a sample. In the method, the relative expression quantity of RRM1mRNA in the sample can be quantitatively detected by use of the real-time fluorescence quantification PCR (polymerase chain reaction) technology. The invention provides a primer and a probe for quantitatively detecting the relative expression quantity of RRM1 mRNA in the sample, wherein the primer and the probe comprise upstream and downstream primers RRM1-F / RRM1-R and a probe RRM1-Probe for detection as well as upstream and downstream primers Actin-F / Actin-R and a probe Actin-Probe for a house-keeping gene actin. The invention also provides a kit for quantitatively detecting the relative expression quantity of RRM1 mRNA in the sample. By calculating the ratio of the expression quantity of RRM1 in the sample obtained by the method to the normal base of a healthy person, obtained by statistics, the relative expression quantity of RRM1 mRNA is obtained, the detection time can be effectively saved, and the detection accuracy is improved.
Owner:JILIN ADICON CLINICAL LAB

Target spot selecting method for efficiently inhibiting WSSV (White Spot Syndrome Virus)

The invention relates to a target spot selecting method for efficiently inhibiting WSSV (White Spot Syndrome Virus), which comprises the steps of: 1, selecting coded sequences of ribonucleotide reductase and DNA polymerase in a WSSV genome; 2, generating a WSSV-resistant small RNA interference molecule by using software; and 3, screening theoretically efficient WSSV-resistant siRNA (small interfering RNA) according to a siRNA design rule. The small RNA molecule is designed by using the target spot selecting method, thus the selection range of the virus-resistant small RNA molecule can be effectively narrowed, the working efficiency is increased, the research cost is remarkably lowered, and the popularization and the application of an RNA interference technology in the aquatic virus-resistant field are facilitated.
Owner:EAST CHINA SEA FISHERIES RES INST CHINESE ACAD OF FISHERY SCI

Sulfonamide Compound or Salt Thereof

The present invention provides a novel sulfonamide compound having a ribonucleotide reductase inhibitory activity or a salt thereof, and a pharmaceutical composition containing the same as an active ingredient.A compound represented by Formula (I) [wherein, X1 represents an oxygen atom or the like; X2 represents an oxygen atom; X3 represents —NH—; X4 represents a hydrogen atom or the like; R1 represents —C(R11)(R12)— or the like; R11 and R12 are the same or different and each represents a hydrogen atom or the like; R2 represents an optionally substituted C6-C14 aromatic hydrocarbon group or the like; R3 represents an optionally substituted C6-C14 aromatic hydrocarbon group or the like; R4 represents a hydrogen atom or the like] or a salt thereof.
Owner:TAIHO PHARMA CO LTD

Cordyceps sinensis ribonucleotide reductase as well as coding gene and application thereof

The invention relates to ribonucleotide reductase from 'Bailing' producing strain cordyceps sinensis hirsutella sinensis for anabolism of deoxidized pyrimidine nucleoside diphosphate from pyrimidine nucleoside diphosphate, a gene coding the ribonucleotide reductase and application of the ribonucleotide reductase. The ribonucleotide reductase has over 90% of homology to the amino acid sequence shown by SEQ ID No.1 or SEQ ID No.3; and the coding gene has over 90% of homology to the nucleotide sequence shown by SEQ ID No.2 or SEQ ID No.4. According to the invention, the metabolic pathway for synthesizing deoxidized pyrimidine nucleoside diphosphate from pyrimidine nucleoside diphosphate is studied in details in principle, the cloning DNA (Deoxyribonucleic Acid) comprising the nucleotide sequence provided by the invention can be transferred into engineering bacteria through transduction, transformation and combined transfer, high expressivity of the host deoxidized pyrimidine nucleoside diphosphate is obtained by adjusting the expression of the deoxidized pyrimidine nucleoside diphosphate biosynthesis gene, an effective means of increasing output of the deoxidized pyrimidine nucleoside diphosphate is provided, and a significant application prospect is realized.
Owner:ZHEJIANG UNIV OF TECH +1

Synthetic method of beta-thymidine

The invention discloses a synthetic method of beta-thymidine. Thymidine is synthesized reversely by adopting enzyme engineering, glucose dehydrogenase, uridine kinase, inkfish pyruvate kinase, ribonucleotide reductase, thymidylate kinase and thymidine kinase are used, 5-methyluridine is used as a raw material, nucleotide is generated through two phosphorylation steps and then is converted into deoxynucleotide, and then the thymidine is generated through two-step dephosphorylation. According to the synthetic method of beta-thymidine disclosed by the invention, the cost is greatly reduced, the production cycle is shortened, the industrial waste is reduced, and the beta-thymidine is non-toxic and environmentally-friendly.
Owner:SUZHOU DUMEI BIOTECH CO LTD

Method, kit, primers and probes for detecting relative expression of rrm1 mRNA

The invention provides a method for quantitatively detecting the relative expression quantity of RRM1 (ribonucleotide reductase M1) mRNA (messenger ribonucleic acid) in a sample. In the method, the relative expression quantity of RRM1mRNA in the sample can be quantitatively detected by use of the real-time fluorescence quantification PCR (polymerase chain reaction) technology. The invention provides a primer and a probe for quantitatively detecting the relative expression quantity of RRM1 mRNA in the sample, wherein the primer and the probe comprise upstream and downstream primers RRM1-F / RRM1-R and a probe RRM1-Probe for detection as well as upstream and downstream primers Actin-F / Actin-R and a probe Actin-Probe for a house-keeping gene actin. The invention also provides a kit for quantitatively detecting the relative expression quantity of RRM1 mRNA in the sample. By calculating the ratio of the expression quantity of RRM1 in the sample obtained by the method to the normal base of a healthy person, obtained by statistics, the relative expression quantity of RRM1 mRNA is obtained, the detection time can be effectively saved, and the detection accuracy is improved.
Owner:JILIN ADICON CLINICAL LAB
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