66 results about "Nucleoside phosphorylase" patented technology

The present invention relates to compounds of the general formula (I) which are inhibitors of purine nucleoside phosphorylases (PNP), purine phosphoribosyltransferases (PPRT), 5′-methylthioadenosine phosphorylases (MTAP), 5′-methylthioadenosine nucleosidases (MTAN) and / or nucleoside hydrolases (NH). The invention also relates to the use of these compounds in the treatment of diseases and infections including cancer, bacterial infections, protozoal infections, and T-cell mediated disease and to pharmaceutical compositions containing the compounds.

The invention provides a compound of the formula:wherein A is selected from N, CH and CR; R is selected from halogen, optionally substituted alkyl, aralkyl and aryl, OH, NH2, NHR1, NR1R2 and SR3; R1, R2 and R3 are each optionally substituted alkyl, aralkyl or aryl groups; B is selected from NH2 and NHR4; R4 is an optionally substituted alkyl, aralkyl or aryl group; X is selected from H, OH and halogen; Z is selected from H, Q, SQ and OQ; Q is an optionally substituted alkyl, aralkyl or aryl group; or a tautomer, a pharmaceutically acceptable salt, an ester, or a prodrug thereof; with the proviso that the stereochemistry of the aza-sugar moiety is D-ribo or 2′-deoxy-D-erythro-; pharmaceutical compositions comprising said compound; and methods of treatment using said compound.

The present invention relates to compounds of the general formula (I) which are inhibitors of purine muclioside phosphorylases (PNP), purine phosphoribosyltransferases (PPRT), 5′-methylthioadenosine phosphorylases (MTAP), 5′-methylthioadenosine mucliosidases (MTAN) and / or nucleoside hydrolases (NH). The invention also relates to the use of these compounds in the treatment of diseases and infections including cancer, bacterial infections, protozoal infections, and T-cell mediated disease and to pharmaceutical compositions containing the compounds.

The present invention relates to compounds of the general formula (I) which are inhibitors of purine nucleoside phosphorylases (PNP), purine phosphoribosyltransferases (PPRT), 5′-methylthioadenosine phosphorylases (MTAP), 5′-methylthioadenosine nucleosidases (MTAN) and / or nucleoside hydrolases (NH). The invention also relates to the use of these compounds in the treatment of diseases and infections including cancer, bacterial infections, protozoal infections, and T-cell mediated disease and to pharmaceutical compositions containing the compounds.

The present invention relates to a new process for the preparation of compounds of general formula (I) which are inhibitors of purine nucleoside phosphorylases (PNP), purine phosphoribosyltransferases (PPRT), 5′-methylthioadenosine phosphorylases (MTAP), 5′-methylthioadenosine nucleosidases (MTAN) and / or nucleoside hydrolases (NH). The present invention relates to a new process for the preparation of compounds of general formula (I) which are inhibitors of purine nucleoside phosphorylases (PNP), purine phosphoribosyltransferases (PPRT), 5′-methylthioadenosine phosphorylases (MTAP), 5′-methylthioadenosine nucleosidases (MTAN) and / or nucleoside hydrolases (NH).

The present invention relates to a new process for the preparation of compounds of general formula (I) which are inhibitors of purine nucleoside phosphorylases (PNP), purine phosphoribosyltransferases (PPRT), 5′-methylthioadenosine phosphorylases (MTAP), 5′-methylthioadenosine nucleosidases (MTAN) and / or nucleoside hydrolases (NH). The present invention relates to a new process for the preparation of compounds of general formula (I) which are inhibitors of purine nucleoside phosphorylases (PNP), purine phosphoribosyltransferases (PPRT), 5′-methylthioadenosine phosphorylases (MTAP), 5′-methylthioadenosine nucleosidases (MTAN) and / or nucleoside hydrolases (NH).

The invention relates to the fields of biotechnology and biological medicine, in particular to a pyrimidine nucleoside phosphorylase gene and the application thereof. The nucleotide sequence of the pyrimidine nucleoside phosphorylase gene is shown in SEQ ID NO.1, and the amino acid sequence of pyrimidine nucleoside phosphorylase coded by the gene is shown in SEQ ID NO.2. A genetically engineered bacterium containing the gene is obtained by transferring the gene into escherichia coli. By culturing the genetically engineered bacterium and optimizing the fermentation technology, large-scale production of recombined pyrimidine nucleoside phosphorylase is achieved, and the recombined pyrimidine nucleoside phosphorylase can be used for catalyzed synthesis of Sofosbuvir midbody (2'R)-2'-deoxygenation-2'-fluorine-2'-methyl uridine and production of other nucleoside bulk pharmaceutical chemicals and medical intermediates.

A host cell stably transformed or transfected by a vector including a DNA sequence encoding for mutant purine nucleoside cleavage enzymes is provided. The transformed or transfected host cell can be used in combination with a purine substrate to treat tumor cells and / or virally infected cells. A nucleotide sequence encoding mutant E. coli derived purine nucleoside phosphorylase proteins which can be used in conjunction with an appropriate substrate to produce toxins which impair abnormal cell growth is also provided. A method is detailed for the delivery of toxin by generation within target cells or by administration and delivery to the cells from without. Novel purine nucleosides are detailed that yield a cytotoxic purine upon enzymatic cleavage. A synthetic process for nucleosides is also detailed.

The invention relates to purine nucleoside phosphorylase and a preparation method of the purine nucleoside phosphorylase, in particular to a mutational pseudoalteromonas-genus purine nucleoside phosphorylase. Compared with a wild-type amino acid sequence, the amino acid sequence of the mutational purine nucleoside phosphorylase is characterized in that Asp at the 98th bit is mutated into Tyr. The invention further discloses the preparation method of the purine nucleoside phosphorylase. The purine nucleoside phosphorylase and the preparation method of the purine nucleoside phosphorylase have the advantages of being high in yield and good in heat stability. The invention further discloses polynucleotide for encoding the amino acid sequence of the purine nucleoside phosphorylase, a carrier containing the polynucleotide and a host cell containing the polynucleotide.

The invention discloses a preparation method of vidarabine monophosphate. The method first prepares genetically engineered bacterium with co-expression of purine nucleoside phosphorylase and uridine phosphorylase, and then uses the genetically engineered bacterium to prepare vidarabine monophosphate. The method is characterized in that coexpression of purine nucleoside phosphorylase and uridine phosphorylase is realized in genetically engineered bacterium by using a molecular cloning method, so as to obtain vidarabine biotransformation bacteria with high enzyme specific activity; the thalli obtained by the invention is used to produce vidarabine; and the reaction substrate concentration can be increased to more than 100 mM, the reaction conversion rate is more than 90%, the dosage of reaction thalli is less than 0.3% (thalli wet weight / reaction volume ml), and reaction time is shortened to 6 h.

The invention discloses a production process for producing antiviral medicament ribavirin through a bacillus amyloliquefaciens precursor TCA addition (1, 2, 4-triazole-3-carboxyformamide) fermentation method. The process comprises the following steps: establishing recombinant plasmid pBSA43-Bs816PNP which can be stably replicated in bacillus amyloliquefaciens cells and efficiently secretes and expresses purine nucleoside phosphorylase (PNPase); converting the plasmid into vernine for producing the bacillus amyloliquefaciens TA208, thereby obtaining a genetically engineered bacterium RBVM (pBSA43-Bs816PNP) with the two characteristics of high-efficiency production and high-efficiency expression of PNPase. By adoption of the genetically engineered bacterium, by taking glucose, yeast extract, bean concentrate, corn steep liquor, monopotassium phosphate, magnesium sulfate, ferrous sulfate and running water as raw materials, the precursor TCA is added for fermenting, and high-concentration ribavirin can be detected in the culture medium after the precursor is added within several hours. The process has the advantages of short fermentation period, high yield, high glucoside conversion rate, easy and convenient process, low cost, low energy consumption, slight pollution and the like.

A desired isomer is selectively prepared by phosphorolyzing and isomerizing an anomer mixture of a 1-phosphorylated saccharide derivative while crystallizing one of the isomers to displace the equilibrium. Furthermore, using the action of a nucleoside phosphorylase, a nucleoside is prepared from the 1-phosphorylated saccharide derivative obtained and a base with improved stereoselectivity and a higher yield. This process is an anomer-selective process for preparing a 1-phosphorylated saccharide derivative and a nucleoside.

The invention discloses a production process for producing antiviral medicament ribavirin through a bacillus amyloliquefaciens precursor TCA addition (1, 2, 4-triazole-3-carboxyformamide) fermentation method. The process comprises the following steps: establishing recombinant plasmid pBSA43-Bs816PNP which can be stably replicated in bacillus amyloliquefaciens cells and efficiently secretes and expresses purine nucleoside phosphorylase (PNPase); converting the plasmid into vernine for producing the bacillus amyloliquefaciens TA208, thereby obtaining a genetically engineered bacterium RBVM (pBSA43-Bs816PNP) with the two characteristics of high-efficiency production and high-efficiency expression of PNPase. By adoption of the genetically engineered bacterium, by taking glucose, yeast extract, bean concentrate, corn steep liquor, monopotassium phosphate, magnesium sulfate, ferrous sulfate and running water as raw materials, the precursor TCA is added for fermenting, and high-concentration ribavirin can be detected in the culture medium after the precursor is added within several hours. The process has the advantages of short fermentation period, high yield, high glucoside conversion rate, easy and convenient process, low cost, low energy consumption, slight pollution and the like.

The invention relates to the enzymatic production of cytosinic nucleoside analogues. In particular it relates to a new synthesis process of cytosine nucleoside analogues by using nucleoside phosphorylase enzymes, particularly Pyrimidin Nucleoside Phosphorylases (PyNPs) or mixtures of Purine Nucleoside Phosphorylases (PNPs) and PyNPs.

The invention relates to compounds of the general formula (I) which are inhibitors of purine nucleoside phosphorylases (PNPs) and / or nucleoside hydrolases (NHs). The invention also relates to the use of these compounds in the treatment of diseases and infections including cancer, bacterial infections, protozoal infections, and T-cell mediated disease and to pharmaceutical compositions containing the compounds.