Abstract: A method of purifying cytidine diphosphate choline, which comprises contacting a cytidine diphosphate choline solution containing a nucleic acid analogue and having a pH of not less than 0.5 and not more than 5.0 with an H-type strongly acidic cation exchange resin, and eluting cytidine diphosphate choline adsorbed onto the resin with water or an aqueous solution having an ion concentration of not more than 0.1 mol/L to separate and purify the cytidine diphosphate choline.

Abstract: The invention provides a method of producing a chemical product through continuous fermentation which includes filtering a culture of a microorganism or cultured cells with a separation membrane to recover a product from a filtrate and simultaneously retaining a nonfiltered fluid in, or refluxing it to, the culture, and adding fermentation materials to the culture, wherein a porous membrane having an average pore size of 0.01 ?m or more to less than 1 ?m is used as the separation membrane and the filtration is conducted with a transmembrane pressure difference in the range of 0.1 to 20 kPa. According to this method, the fermentation productivity of the chemical product can be largely elevated at high stability and a low cost.

Abstract: The invention discloses a series of Methanococcus jannaschii S-adenosylmethionine synthetase mutants with improved thermostability and high catalytic activity obtained by using gene mutation technique, characterized in that these mutants refer to an enzyme using Sequence 2 in the Sequence Listing as the reference sequence and contains at least one mutation at position 102, position 93, position 230, and position 357 and has a catalytic activity at least 70% higher than that of the wild-type S-adenosylmethionine synthetase using adenosine triphosphate (ATP) and methionine as substrates. These S-adenosylmethionine synthetase mutants can be used in the production of S-adenosylmethionine.

Abstract: A purine-derived substance is produced by culturing a Bacillus bacterium which has an ability to produce a purine-derived substance and has enhanced activity of an enzyme of the oxidative pentosephosphate pathway. The purine-derived substance is produced in the medium or the bacterial cells, and can be collected from the medium or the bacterial cells.

Abstract: A purine-derived substance is produced by culturing a bacterium belonging to the genus Bacillus which is able to produce purine-derived substance and has been modified so that enzymatic activity of fructose bisphosphatase is decreased, and collecting the purine-derived substance from the medium or cells.

Abstract: Herein described are prodrugs activated by RNA-dependent DNA-polymerases, such as telomerase and retroviral reverse transcriptases, their use for the treatment of haematological tumours and of blood and blood derivatives from patients affected by retroviral infections, and their use for the preparation of pharmaceutical compositions, to be used for the treatment of solid tumours, of precancerous states and of diseases caused by infection with retroviruses.

Abstract: A process for the fermentative production of at least one organic compound having at least 3 C atoms or having at least 2 C atoms and at least one 1 N atom, comprising the following steps: a1) milling a starch feedstock, thus obtaining a millbase which comprises at least part of the nonstarchy solid constituents of the starch feedstock; a2) suspending the millbase in an aqueous liquid and hydrolysis of the starch portion in the millbase by enzymatic liquefaction and, if appropriate, subsequent saccharification, whereby a first liquid (1) which comprises mono- or oligosaccharides is obtained; and b) addition of the liquid (1) which comprises mono- or oligosaccharides together with metabolizable mono-, di- or oligosaccharides or together with a composition which comprises metabolizable mono-, di- or oligosaccharide in a concentration of at least 50% by weight and which is essentially free from solids which are insoluble in water to a fermentation medium comprising a microorganism which is capable of overproduc

Abstract: A microorganism which has a gene encoding an enzyme in which feedback inhibition is desensitized by substitution of one or two amino acids in PRPP amidotransferase encoded by purF of Escherichia coli, a gene encoding a protein which is an inactivated repressor of purine nucleotide biosynthesis encoded by purR, a gene encoding an enzyme which is inactivated purine nucleoside phosphorylase encoded by deoD, a gene encoding an enzyme which is inactivated succinyl-AMP synthase encoded by purA, a gene encoding an enzyme which is inactivated 6-phosphogluconate dehydrase encoded by edd, a gene encoding an enzyme which is inactivated phosphoglucose isomerase encoded by pgi and like is bred and a purine nucleoside is produced by culturing the microorganism.

Abstract: Methods for producing purine nucleosides, and purine nucleotides, such as inosine and 5?-inosinic acid are provided which include using a bacterium belonging to the genus Bacillus or to the genus Escherichia wherein the purine nucleoside productivity of said bacterium is enhanced by increasing an activity of the YdhL protein. Also disclosed is the amino acid sequence of the YdhL protein from Bacillus amyloliquefaciens and the gene encoding it.

Abstract: A target substance is produced by culturing a bacterium which has the ability to produce the target substance in a medium to cause accumulation of said target substance in the medium and collecting the target substance from the medium, wherein the bacterium is modified so that a system for uptake of a byproduct of the target substance or a substrate for a biosynthesis system of the target substance into the bacterial cell.

Abstract: The present invention relates to a method for the in vitro enzymatic synthesis of deoxyribonucleosides and enzymes suitable for this method.

Abstract: A glyoxal-guanosine-group compound is prepared either by reacting glyoxal-guanine with any one of ribose-1-phosphate and 2-deoxyribose-1-phosphate in the presence of purine nucleoside phosphorylase, or by reacting glyoxal-guanine with any one selected from the group consisting of uridine, 2?-deoxyuridine and thymidine, together with phosphate ion, in the presence of purine nucleoside phosphorylase and pyrimidine nucleoside phosphorylase. The glyoxal-guanosine-group compound is then decomposed by alkali, whereby a guanosine-group compound consisting of guanosine and 2?-deoxyguanosine is prepared.

Abstract: A glyoxal-guanosine-group compound is prepared either by reacting glyoxal-guanine with any one of ribose-1-phosphate and 2-deoxyribose-1-phosphate in the presence of purine nucleoside phosphorylase, or by reacting glyoxal-guanine with any one selected from the group consisting of uridine, 2?-deoxyuridine and thymidine, together with phosphate ion, in the presence of purine nucleoside phosphorylase and pyrimidine nucleoside phosphorylase. The glyoxal-guanosine-group compound is then decomposed by alkali, whereby a guanosine-group compound consisting of guanosine and 2?-deoxyguanosine is prepared.

Abstract: A glyoxal-guanosine-group compound is prepared either by reacting glyoxal-guanine with any one of ribose-1-phosphate and 2-deoxyribose-1-phosphate in the presence of purine nucleoside phosphorylase, or by reacting glyoxal-guanine with any one selected from the group consisting of uridine, 2?-deoxyuridine and thymidine, together with phosphate ion, in the presence of purine nucleoside phosphorylase and pyrimidine nucleoside phosphorylase. The glyoxal-guanosine-group compound is then decomposed by alkali, whereby a guanosine-group compound consisting of guanosine and 2?-deoxyguanosine is prepared.

Abstract: The invention provides methods of screening for substances having an effect on a nicotine receptor by contacting a cell having a nicotine receptor with a test substance; and determining any increase or decrease in phosphorylation of Janus-Activated Kinase 2 (JAK2). An increase in phosphorylation of JAK2 indicates that the test substance stimulates the nicotine receptor, and wherein a decrease in phosphorylation of JAK2 indicates that the test substance inhibits the nicotine receptor. The invention also provides screening methods for identification of substances that affect nicotine receptor activity through activity mediated by the AT2 receptor. Related pharmaceutical compositions and methods of treatment are also provided.

Abstract: 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.

Abstract: A 2′-deoxyribonucleoside is produced by culturing a microorganism, which is transformed with a gene encoding a ribonucleotide reductase and in which 2′-deoxyribonucleoside degradation activity is decreased or eliminated by disrupting a gene encoding a purine nucleoside phosphorylase on chromosomal DNA, in a medium in which the microorganism can grow to produce the 2′-deoxyribonucleoside.

Abstract: The invention is a process for stereoselectively producing a dioxolane nucleoside analogue from an anomeric mixture of &bgr; and &agr; anomers represented by the following formula A or formula B: wherein R is selected from the group consisting of C1-6 alkyl and C6-15 aryl and Bz is benzoyl. The process comprises hydrolyzing said mixture with an enzyme selected from the group consisting of Protease N, Alcalase, Savinase, ChiroCLEC-BL, PS-30, and ChiroCLEC-PC to stereoselectively hydrolyze predominantly one anomer to form a product wherein R1 is replaced with H. The process also includes the step of separating the product from unhydrolyzed starting material. Additionally, the functional group at the C4 position is stereoselectively replaced with a purinyl or pyrimidinyl or derivative thereof.

Abstract: This invention relates to the production of new & stable salts of S-adenosyl-L-methionine SAMe). The source of SAMe used in the salt formation is from chemical process wherein stereoselective methylation of S-adenosyl-L-homocysteine is achieved. The process for the salt preparation is simple, efficient & reproducible on large scale. The new salts were found to be stable at accelerated temperature for minimum 3 months.

Abstract: Stable salts of S-adenosyl-1-methionine with polycations such as chitosan are described. The salts according to the invention are very stable and are valuable for use as active constituents in pharmaceutical compositions.

Abstract: A glyoxal-guanosine-group compound is prepared either by reacting glyoxal-guanine with any one of ribose-1-phosphate and 2-deoxyribose-1-phosphate in the presence of purine nucleoside phosphorylase, or by reacting glyoxal-guanine with any one selected from the group consisting of uridine, 2′-deoxyuridine and thymidine, together with phosphate ion, in the presence of purine nucleoside phosphorylase and pyrimidine nucleoside phosphorylase. The glyoxal-guanosine-group compound is then decomposed by alkali, whereby a guanosine-group compound consisting of guanosine and 2′-deoxyguanosine is prepared.

Abstract: The production of a purified extracellular bacterial signal called autoinducer-2 is regulated by changes in environmental conditions associated with a shift from a free-living existence to a colonizing or pathogenic existence in a host organism. Autoinducer-2 stimulates LuxQ luminescence genes, and is believed also to stimulate a variety of pathogenesis related genes in the bacterial species that produce it. A new class of bacterial genes is involved in the biosynthesis of autoinducer-2.

Abstract: The invention is a process for stereoselectively producing a dioxolane nucleoside analogue from an anomeric mixture of &bgr; and &agr; anomers represented by the following formula A or formula B: wherein R is selected from the group consisting of C1-6 alkyl and C6-15 aryl and Bz is benzoyl. The process comprises hydrolyzing said mixture with an enzyme selected from the group consisting of Protease N, Alcalase, Savinase, ChiroCLEC-BL, PS-30, and ChiroCLEC-PC to stereoselectively hydrolyze predominantly one anomer to form a product wherein R1 is replaced with H. The process also includes the step of separating the product from unhydrolyzed starting material. Additionally, the functional group at the C4 position is stereoselectively replaced with a purinyl or pyrimidinyl or derivative thereof.

Abstract: The invention relates to a pentopyranosylnucleoside of the formula (I) or of the formula (II) their preparation and use for the production of a therapeutic, diagnostic and/or electronic component.

Abstract: A 2′-deoxyribonucleoside is produced by culturing a microorganism, which is transformed with a gene encoding a ribonucleotide reductase and in which 2′-deoxyribonucleoside degradation activity is decreased or eliminated by disrupting a gene encoding a purine nucleoside phosphorylase on chromosomal DNA, in a medium in which the microorganism can grow to produce the 2′-deoxyribonucleoside.

Abstract: Xanthosine-5′-monophosphate is produced by cultivating the bacterium which has a resistance to growth inhibition by an inhibitor selected from the group consisting of inhibitors of cell membrane biosynthesis and/or functioning, phosphorylation inhibitors, uncoupling agents, RNA-polymerase inhibitors and methionine analogs, and has an ability to produce xanthosine-5′-monophosphate according to produce and accumulate xanthosine-5′-monophosphate in the culture, and recovering the xanthosine-5′-monophosphate therefrom.

Abstract: The present invention provides isolated modified inosine 5′-monophosphate dehydrogenase (IMPDH) polypeptides. These modified IMPDH polypeptides comprise a substitute oligo-peptide that replaces the subdomain region. The modified polypeptides of the invention bind to an inhibitor, such as MPA, and/or exhibit functional activity of wild-type IMPDH holo-enzyme.

Abstract: This invention relates to a process for producing a sugar nucleotide, in which a) a culture broth of a microorganism capable of producing NTP from a nucleotide precursor, or a treated product of the culture broth, and b) a culture broth of a microorganism capable of producing a sugar nucleotide from a sugar and NTP, or a treated product of the culture broth, are used as enzyme sources; a process for producing a complex carbohydrate, in which the above-described a) and b) and c) a culture broth of a microorganism, an animal cell or an insect cell capable of producing a complex carbohydrate from a sugar nucleotide and a complex carbohydrate precursor, or a treated product of the culture broth, are used as enzyme sources; a process for producing a complex carbohydrate, in which a culture broth of a microorganism, an animal cell or an insect cell capable of producing a complex carbohydrate from a sugar nucleotide and a complex carbohydrate precursor, or a treated product of the culture broth, is as an enzyme sour

Abstract: The present invention relates to a process for the preparation of pharmaceutically acceptable salts of (SS,RS)-S-adenosyl-L-methionine and allows to obtain the salified (RS)-(+)-S-adenosyl-L-methionine diastereoisomer in amounts lower than or equal to 3% with respect to the salified (SS)-(+)-S-adenosyl-L-methionine diastereoisomer; the salts that can be obtained by the process of the invention keep their configuration stable in time.

Abstract: The present invention relates to a method of screening for drug binding to serum proteins by: preparing at least two solutions each including a concentration of a serum protein and a concentration of a candidate drug, wherein the concentration of the candidate drug is different for each of the at least two solutions; exposing each of the at least two solutions to a light source; measuring fluorescent emission by the serum protein or a serum protein-candidate drug complex for each of the at least two solutions upon said exposing; and determining whether a change in fluorescence emission is measured for an increased concentration of the candidate drug, wherein the change in fluorescence emission indicates binding of the candidate drug to the serum protein. A kit useful for performing a fluorimetric screening of drug binding to serum proteins is also disclosed.

Abstract: A process for converting uridines to 2′,3′-dideoxy-2′,3′-didehydrouridines by reacting acetic anhydride with a 2′,3′-0-alkoxymethylideneuridine intermediate.

Abstract: A method of reducing the percentage of Epstein-Barr virus genome-carrying cells which exhibit Epstein-Barr virus early antigen induction, where the Epstein-Barr virus genome-carrying cells have been cultivated in the presence of at least one tumor-promoting or tumor-inducing chemical. The method is carried out by cultivating Epstein-Barr virus genome-carrying cells in the presence of a tumor-promoting or tumor-inducing chemical; and treating the Epstein-Barr virus genome-carrying cells with a synthetic fluorescein dye. The dyes effectively reduce the incidence of Epstein-Barr virus early antigen induction in the cultivated Epstein-Barr virus genome-carrying cells.

Abstract: A nucleoside/tide compound having the structure NUC-L-S-LB/LG is described wherein NUC is a nucleoside/tide having a nucleobase portion B, L is a rigid linkage, S is a spacer; and LB/LG is a member of a linkage pair or a label. NUC is attached to L through B such that when B is a purine, L is attached to the 8-position of the purine, when B is 7-deazapurine, L is attached to the 7-position of the 7-deazapurine, and when B is pyrimidine, L is attached to the 5-position of the pyrimidine. In an important aspect of the invention, L has the structure wherein each of n, o and p are integers ranging from 0 to 3, and the sum of n, o and p is at least 2, and each of W, X, Y and Z is selected from the group consisting of carbon and nitrogen. The invention further includes polynucleotide compounds comprising the nucleoside/tide, and primer extension methods utilizing the nucleoside/tide, particularly when used in combination with certain mutant polymerase enzymes.

Abstract: A process for preparing 2,6-diaminopurine-2′-deoxyriboside and 2′-deoxyguanosine. These compounds may be used as materials for pharmaceuticals, such as antiviral agents and the like, and particularly as starting materials for antisense oligonucleotides.

Abstract: Oligonucleotides and other macromolecules are provided which have increased nuclease resistance, substituent groups (such as 2′-aminooxy groups) for increasing binding affinity to complementary strand, and subsequences of 2′-deoxy-erythro-pentofuranosyl nucleotides that activate RNase H. Such oligonucleotides and macromolecules are useful for diagnostics and other research purposes, for modulating the expression of a protein in organisms, and for the diagnosis, detection and treatment of other conditions susceptible to oligonucleotide therapeutics.

Abstract: The invention relates to a multifunctional nucleoside didesoxyribosyl or nucleoside deoxyribosyl transferase which has one or more of the following additional activities (desoxy) nucleoside kinase, nucleoside reductase desaminase, or DNA polymerase activity. Utilizing the multifunctional enzyme results in a variety of nucleic acid products. These products can be prepared using sequential reactions in a single batch process wherein the sequential reaction can be caused to occur by varying process conditions in a manner which turns on or off the requisite activities causing the sequential reactions to occur. An example of a product prepared in this manner is dideoxyribofuranoside triphosphate. Certain of the resultant products have pharmaceutical activities, e.g. antiviral agents. Lactobacillus leichmannii (DSM 20076) is a source of the multifunctional nucleoside deoxyribosyl transferase.

Abstract: A process for preparing a sugar nucleotide from a nucleotide by using a yeast cell, characterized in that both a nucleoside diphosphate-sugar pyrophosphorylase and a sugar 1-phosphate are present in the reaction system. According to this process, various sugar nucleotides, which have been prepared only in low productivity by the conventional yeast cell process, can be efficiently prepared.

Abstract: The present invention provides a method of preparing stably and at a high yield a purine nucleoside compound by utilizing an exchange reaction of a nucleic acid base which is carried out in the presence of an enzyme, and also provides a microorganism capable of producing uracil thymine dehydrogenase or dihydrouracil dehydrogenase. In preparing the purine nucleoside compound, a pyrimidine nucleoside compound and a purine base are subjected to a base exchange reaction in an aqueous solution containing phosphate ions in the presence of pyrimidine nucleoside phosphorylase and purine nucleoside phosphorylase. The pyrimidine base formed by the base exchange reaction is converted by a microorganism or an enzyme derived from the microorganism into a compound incapable of acting as substrates of pyrimidine nucleoside phosphorylase and purine nucleoside phosphorylase so as to obtain a desired product of purine nucleoside compound.

Abstract: A nucleoside/tide compound having the structureNUC--L--S--LB/LGis described wherein NUC is a nucleoside/tide having a nucleobase portion B, L is a rigid linkage, S is a spacer; and LB/LG is a member of a linkage pair or a label. NUC is attached to L through B such that when B is a purine, L is attached to the 8-position of the purine, when B is 7-deazapurine, L is attached to the 7-position of the 7-deazapurine, and when B is pyrimidine, L is attached to the 5-position of the pyrimidine. In an important aspect of the invention, L has the structure ##STR1## wherein each of n, o and p are integers ranging from 0 to 3, and the sum of n, o and p is at least 2, and each of W, X, Y and Z is selected from the group consisting of carbon and nitrogen. The invention further includes polynucleotide compounds comprising the nuclcoside/tide, and primer extension methods utilizing the nucleoside/tide, particularly when used in combination with certain mutant polymerase enzymes.

Abstract: A solid phase synthesis reaction vessel includes a vessel with a first inlet, a second inlet, and an outlet. A first stopcock is disposed within the first inlet and a second stopcock is disposed within the outlet. Solid phase material is prevented from escaping the reaction vessel via the outlet while allowing fluid to flow through the outlet by a frit. In one embodiment, the reaction vessel includes an outer hollow shell surrounding the vessel to allow cooling or heating fluid to flow therein for controlling the temperature in the interior reaction volume. The solid phase synthesis reaction vessel provides for the independent opening and closing of each of the inlets and outlet to provide for various ways of draining the vessel, varying the conditions within the vessel, and/or adding additional materials into the vessel.

Abstract: Miniaturized, self-contained apparatus for conducting bio-chemical reactions and analyses is formed in a compact structure made from a substrate which includes a plurality of reaction chambers and a plurality of analysis chambers which are in fluid communication with the reaction chambers. Independently controllable heaters and coolers are positioned in thermal contact with the reaction chambers to permit parallel processing of biological samples at different temperature cycles. The apparatus is especially useful for performing and analyzing the results of a polymerase chain reaction.

Abstract: The present invention relates to the genes for riboflavin biosynthesis in the fungus Ashbya gossypii and to genetic engineering processes for preparing riboflavin using these genes and gene products.

Abstract: A computer system chassis, including a base and a cover, implements an improved grounding system by integrally forming a plurality of flexible protruding contacts into predetermined contact regions throughout the base during the metal punching manufacturing phase of the chassis base blank. In this way, when the base and cover are attached to each other, the size of any gaps which may form in these contact regions, as a result of warpage or design tolerances, are reduced. This is due to the number of mechanical contacts being made by the plurality of flexible contacts which protrude and extend across these gaps and connect the base to the cover. In addition to reducing the size of these gaps, the flexible contacts provide an improved electrical grounding to the cover by increasing metal-to-metal contact between the cover and the base, both of which reduce EMI emissions from the computer system chassis.

Abstract: Substituted propargylethoxyamido nucleosides are disclosed having the structure ##STR1## wherein X is selected from the group consisting of amino alkanoic acid, alkylamino benzoic acid, .alpha.-amino acid, and 4-amino-2-butynoic acid. R.sub.1 and R.sub.2 taken separately are selected from the group consisting of --H, lower alkyl, protecting group, and label; R.sub.3 is selected from the group consisting of --H and lower alkyl. B is a 7-deazapurine, purine, or pyrimidine nucleoside base. When B is purine or 7-deazapurine, the sugar moiety is attached at the N.sup.9 -position of the purine or deazapurine, and when B is pyrimidine, the sugar moiety is attached at the N.sup.1 -position of the pyrimidine.

Abstract: The individual enantiomers of the compounds (Ia), (Ib), (IIa) or (IIb), optionally substituted by non-interfering substituent(s). The novel enantiomers can be obtained by biotransformation. The (Ia) or (IIa) compounds can be used for the synthesis of chiral carbocyclic nucleosides.

Abstract: A process for the production of arabinonucleotides of general formula I ##STR1## in which X represents a hydrogen atom or a fluorine atom, is described, which is characterized in that an arabinonucleoside of general formula II ##STR2## in which X has the above-mentioned meaning, is fermented in the presence of an aryl phosphate of general formula III ##STR3## in which Y symbolizes a hydrogen atom or a nitro group andZ symbolizes two hydrogen atoms or two alkali metal atoms,with a microorganism that is capable of phosphorylating nucleosides.

Abstract: 2',3'-Dideoxy purine nucleosides represented by following general formulae [I] and/or [II] ##STR1## (wherein X and Y indicate nitrogen atoms or carbon atoms and R.sub.1, R.sub.2, R.sub.3, R.sub.4 and R.sub.5 indicate each independently any of hydrogen atom, hydroxyl group, amino group, alkyl group, halogen atom, alkoxy group and mercapto group) are produced by bioconversion with strains of E. coli, K. pneumoniae and E. herbicola.

Abstract: The present invention concerns a process for producing nucleosides by carrying out the reaction of a base donor, a saccharide residue donor and a phosphoric acid donor by the use of an enzyme preparation containing nucleoside phosphorylase, thereby forming an N-glycosidic bond between the base moiety of the base donor and the saccharide moiety of the saccharide residue donor, which comprises using, as the enzyme preparation containing nucleoside phosphorylase, a preparation derived from the cells of one or more kinds of microorganisms belonging to thermophiles of the genus Bacillus and having high nucleoside phosphorylase activity per unit cell weight.

Abstract: Disclosed are methods and compositions of matter for increasing the intracellular synthesis of ATP. The compositions comprise amino acids, metabolites, electrolyte and/or a pentose sugar. When applied to wounds, the invention increases the rate of wound repair and has a antimicrobial effect. When administered orally, the invention increases ATP blood levels and physical performance levels.

Abstract: The present invention concerns a process for producing nucleosides by carrying out the reaction of a base donor, a saccharide residue donor and a phosphoric acid donor by the use of an enzyme preparation containing nucleoside phosphorylase, thereby forming an N-glycosidic bond between the base moiety of the base donor and the saccharide moiety of the saccharide residue donor, which comprises using, as the enzyme preparation containing nucleoside phosphorylase, a preparation derived from the cells of one or more kinds of microorganisms belonging to thermophiles of the genus Bacillus and having high nucleoside phosphorylase activity per unit cell weight.