Abstract: The invention provides a compound of formula I: wherein R1-R6 and X have any of the values described herein, as well as pharmaceutical compostions comprising such compounds and therapeutic methods comprising the administration of such compounds.

Abstract: Liquid microbial starter culture that retains its initial metabolic activity during storage for extended periods of time. Such liquid starter cultures are useful in the manufacturing of food and feed products. Starter cultures of the invention include culture of lactic acid bacteria, e.g. Lactococcus species.

Abstract: The invention is related to phosphorus substituted compounds with antiviral activity, compositions containing such compounds, and therapeutic methods that include the administration of such compounds, as well as to processes and intermediates useful for preparing such compounds.

Abstract: The present disclosure encompasses oligonucleotide aptamers selectively binding a target glycosylated polypeptide or protein, and having biased affinity for the glycan through a boronic acid linked to a nucleosidic base of a nucleotide(s). The disclosure further encompasses methods for isolating an aptamer(s) selectively binding a target glycosylated polypeptide, where, from a population of randomized oligonucleotides that have at least one nucleotide having a boronic acid label linked to a base, is selected a first subpopulation of aptamers binding to the target glycosylated polypeptide or protein. This subpopulation is then amplified without using boronic acid-modified TTP, and amplification products not binding to a target glycosylated polypeptide or protein are selected. The second subpopulation of aptamers is then amplified using boronic acid-modified TTP to provide a population of boronic acid-modified aptamers capable of selectively binding to a glycosylation site of a target polypeptide or protein.

Abstract: Provided herein are compounds, compositions and methods for the treatment of liver disorders, including HCV infections. In one embodiment, compounds and compositions of nucleoside derivatives are disclosed, which can be administered either alone or in combination with other anti-viral agents.

Abstract: Nutritional compositions and methods of making and using the nutritional compositions are provided. In a general embodiment, the present disclosure provides a nutritional composition including one or more exogenous nucleotides.

Abstract: The present invention provides nucleoside compounds and certain derivatives thereof which are inhibitors of RNA-dependent RNA viral polymerase. These compounds are inhibitors of RNA-dependent RNA viral replication and are useful for the treatment of RNA-dependent RNA viral infection. They are particularly useful as inhibitors of hepatitis C virus (HCV) NS5B polymerase, as inhibitors of HCV replication, and/or for the treatment of hepatitis C infection. The invention also describes pharmaceutical compositions containing such nucleoside compounds alone or in combination with other agents active against RNA-dependent RNA viral infection, in particular HCV infection. Also disclosed are methods of inhibiting RNA-dependent RNA polymerase, inhibiting RNA-dependent RNA viral replication, and/or treating RNA-dependent RNA viral infection with the nucleoside compounds of the present invention.

Abstract: This invention relates to novel method of synthesis of RNA utilizing N-2-acetyl protected guanine as nucleoside base, nucleosides, succinates, phosphoramidites, corresponding solid supports that are suitable for oligo deoxy nucleosides and RNA oligonucleotide synthesis. Our discovery using N-acetyl protected guanine as nucleoside base protecting group, which is significantly faster base labile protecting group, yet significantly more stable than commonly utilized -2-isobutyryl guanosine is a novel approach to obtain highest purity oligonucleotides. This approach is designed to lead to very high purity and very clean oligonucleotide, after efficient removal of the protecting groups, including acetyl group from guanine and to produce high purity therapeutic grade DNA oligonucleotides, RNA oligonucleotides, diagnostic DNA, diagnostic RNA for microarray platform.

Abstract: A composition for promoting root nodule formation, which can be easily applied to soil or plants, and enables efficient formation of root nodules, and a method for promoting root nodule formation using the composition are provided. A composition for promoting root nodule formation, which comprises a compound selected from the group consisting of a nucleoside, a nucleotide, and a nucleobase such as inosine, as an active ingredient, is applied to a leguminous plant to promote root nodule formation of the plant.

Abstract: Liquid microbial starter culture that retains its initial metabolic activity during storage for extended periods of time. Such liquid starter cultures are useful in the manufacturing of food and feed products. Starter cultures of the invention include culture of lactic acid bacteria, e.g. Lactococcus species.

Abstract: The invention provides unsaturated phosphonates of Formula I or a tautomer or pharmaceutically accepatble salt thereof, as described herein, as well as pharmaceutical compositions comprising the compounds, and therapeutic methods comprising administering the compounds. The compounds have anti-viral properties and are useful for treating viral infections (e.g. HCV) in animals (e.g. humans).

Abstract: The present invention provides a stable salt of 3?-phosphoadenosine 5?-phosphosulfate (PAPS) and a production method therefor. The present invention is directed to a stable salt of PAPS (amine salt), which is formed between PAPS and an amine compound, and to a method for producing a stable salt of PAPS, which includes adding an amine compound to an aqueous PAPS solution in an amount by mole equal to or greater than that of PAPS, and lyophilizing the resultant solution. The present invention has first realized production of a solid-form PAPS salt having considerably improved stability through a very simple technique. Since the thus-produced amine salt of PAPS is very stable, the salt can be stored or employed without taking much care about decomposition thereof at ambient temperature.

Abstract: The present invention provides a chain-shortened polynucleotide wherein the proportion of a 2′-5′ phosphodiester bond is up to 3% based on the whole phosphodiester bonds or a salt thereof and a pharmaceutical composition containing the same, and a method for producing the same.

Abstract: The present invention provides a method for isolating a double-stranded cDNA having a nucleotide sequence of a complete open reading frame which comprises: (A) admixing (i) an isolated single-stranded cDNA, (ii) a first primer capable of forming a stem-loop structure, comprising (a) at the 3′ end of the primer, a first random sequence, linked to (b) a second sequence, linked to (c) a third sequence which forms a loop structure, linked to (d) a fourth sequence, at the 5′ end of the first primer, which is complementary to the second sequence, under hybridization conditions sufficient for annealing the first sequence of the first primer to the sequence at the 3′ end of the single-stranded cDNA, and (iii) a polymerase; (B) incubating the mixture from step (A) under suitable conditions for DNA synthesis; and (C) performing a polymerase chain reaction by admixing (i) an aliquot of the mixture from (B), (ii) a second primer which specifically binds to the single-stranded cDNA, (iii) a third primer

Abstract: Novel hydrogen-phosphonodithioate compositions are provided which are particularly useful for forming internucleotide and internucleoside linkages in oligonucleosides or oligonucleotides. The oligonucleotides and analogs thereof made by using the hydrogen-phosphonodithioate compositions may be therapeutically useful as antiviral and anticancer agents and may have other therapeutic or diagnostic uses. A method for making the hydrogen-phosphonodithioates is provided as well as a method for converting same to an activated intermediate for substitution on the phosphorus atom.

Abstract: Disclosed are novel bicyclic tris(anhydride)s useful as intermediates in the synthesis of biologically active compounds, and the compounds which may be synthesized from such intermediates.

Abstract: Compounds of formula RS—P(═O)(QR)—Nu where: R is a radical —(CH2)n—W—X; X is a radical —C(═Z)(Y) or —S—U; Z is O or S; W is O or S; Q is O or S; Y and U are an alkyl, aryl or saccharide radical which is optionally substituted with, for example, an OH, SH or NH group; n is equal to 1 to 4, preferably 1 or 2; and Nu is a radical consisting of a residue of a biologically active compound or the dephosphorylated residue of a compound which is biologically active when it bears a phosphate or phosphonate group.

Abstract: The invention provides new methods for synthesizing oligonucleotides that allow for deprotection of the oligonucleotides under more mild conditions than existing methods. The invention further provides a nucleoside base protecting group that is stable under oligonucleotide synthesis conditions, but which can be removed under more mild conditions than existing protecting groups, as well as nucleoside synthons having such base protecting groups.

Abstract: Novel nucleoside or nucleotide analogs comprising 2′-O-amino residues, processes for their synthesis and incorporation into polynucleotides.

Abstract: Propargylethoxyamino nucleosides are disclosed having the structure wherein R1 and R2 are —H, lower alkyl, or label; B is a 7-deazapurine, purine, or pyrimidine nucleoside base; W1 is —H or —OH; W2 is —OH or a moiety which renders the nucleoside incapable of forming a phosphodiester bond at the 3′-position; and W3 is —PO4, —P2O7, —P3O10, phosphate analog, or —OH. Additionally, a primer extension method is provided employing the above propargylethoxyamino nucleosides.

Abstract: The invention provides nucleosides of formulae (I), (II), (V) and (VII) as described in the specification which possess antiviral and anticancer activity. Treatment of breast cancer is a preferred embodiment.

Abstract: A method for detecting disease-associated alleles in patient genetic material is provided whereby a first group of oligonucleotide molecules, synthesized to compliment base sequences of the disease associated alleles is immobilized on a predetermined position on a substrate, and then contacted with patient genetic material to form duplexes. The duplexes are then contacted with a second group of oligonucleotide molecules which are synthesized to extend the predetermined length of the oligonucleotide molecules of the first group, and where each of the oligonucleotide molecules of the second group are tagged and either incorporate universal bases or a mixture of guanine, cytosine, thymine, and adenine, or complementary nucleotide strands that are tagged with a different fluorochrome which radiates light at a predetermined wavelength.

Abstract: This invention presents novel methods for synthesizing phosphorothioate oligonucleotides, using support-bound phosphoramidites. Novel intermediates useful in the methods are also provided.

Abstract: A compound of formula (I) wherein B1 is a radical of a nucleoside base, R1 is hydrogen or a hydroxy-protecting group, R2 is hydrogen, hydroxy or a 2′-nucleoside-modifying atom or group, R3 is an unsubstituted or substituted C1 to C10 alkyl, C2 to C10 alkenyl, C4 to C10 cycloalkylalkyl, C6 to C10 aryl or C7 to C13 aralkyl group, and Z is halogen or a group of formula (II) where R4 and R5 are each independently an unsubstituted or substituted C1 to C10 alkyl, C2 to C10 alkenyl, C4 to C10 cycloalkylalkyl, C6 to C10 aryl or C7 to C13 aralkyl group, or R4 is said group and R5 is hydrogen or R4 and R5 together with the nitrogen atom to which they are attached denote a five- to thirteen-membered heterocyclic ring, or Z is a group of formula (III): Nuc-O—, where Nuc is the residue of a natural or synthetic nucleoside or oligonucleotide after removal of a 5′-hydroxyl group therefrom attached through a 5′-methylene thereof to the indicated oxygen atom.

Abstract: Disclosed are novel bicyclic tris(anhydride)s useful as intermediates in the synthesis of biolologically active compounds, and the compounds which may be synthesized from such intermediates.

Abstract: The present invention concerns a method for generating multiple double stranded nucleic acids by (a) elongating a primer molecule comprising a nucleobase sequence B′ by using one or more nucleotide(s) and a target nucleic acid T that acts as a template for the elongation of said primer such that the elongation product E formed is capable of acting as a template for the elongation of a further primer molecule containing the nucleobase sequence B′; (b) separating the target nucleic acid T from said elongation product E; (c) using said elongation product E as a template for the elongation of a further primer molecule yielding an elongation product E′; and (d) repeating the steps of elongating primer molecules and of separating said elongation products a sufficient number of times to achieve the desired amount of double stranded nucleic acid.

Abstract: A method for the stepwise creation of phosphodiester bonds between desired nucleosides resulting in the synthesis of polynucleotides having a predetermined nucleotide sequence by preparing an initiation substrate containing a free and unmodified 3′-hydroxyl group; attaching a mononucleotide selected according to the order of the predetermined nucleotide sequence to the 3′-hydroxyl of the initiating substrate in a solution containing a catalytic amount of an enzyme capable of catalyzing the 5′ to 3′ phosphodiester linkage of the 5′-phosphate of the mononucleotide to the 3′-hydroxyl of the initiating substrate, wherein the mononucleotide contains a protected 3′-hydroxyl group, whereby the protected mononucleotide is covalently linked to the initiating substrate and further additions are hindered by the 3′-hydroxyl protecting group. Methods in which a mononucleotide immobilized on a solid support is added to a free polynucleotide chain are also disclosed.

Abstract: This invention presents novel methods for synthesizing phosphorothioate oligonucleotides, using support-bound phosphoramiditese. Novel intermediates useful in the methods are also provided.

Abstract: The invention relates to a 3′-substituted nucleoside derivative represented by the following general formula (1): wherein B means a nucleic acid base which may have a substituent, Z represents a lower alkynyl or lower alkenyl group which may be substituted by a group represented by the formula: in which Ra, Rb and Rc are individually a lower alkyl group or a phenyl group, or an oxiranyl group which may have at least one lower alkyl group, R1 and R2 individually represent H or an ester-forming residue capable of easily leaving in a living body, and R3 is H, a mono- or polyphosphoric acid residue, or an ester-forming residue capable of easily leaving in a living body, with the proviso that the sugar moiety is ribose, or a pharmaceutically acceptable salt thereof. The 3′-substituted nucleoside derivative according to the invention has an excellent antitumor activity and is hence useful for treatment for and prevention of cancers.