Abstract: This disclosure relates to the synthesis of novel modified oligonucleotides. The synthesis of novel phosphoramidites are also provided.

Abstract: This invention relates to methods and compositions for administering an effective amount of a CDA substrate drug and an effective amount of cedazuridine. In particular, the invention relates to methods for treating cancer, inhibiting degradation of a CDA substrate drug, and reducing DNA methylation in a subject in need thereof comprising administering an effective amount of a CDA substrate drug and an effective amount of cedazuridine.

Abstract: The present invention relates to a composition comprising as an active ingredient a strain having excellent ability to produce formic acid for preventing or treating obesity or metabolic syndromes caused by obesity; and to a food composition and a health functional food each comprising the active ingredient. The strain having excellent ability to produce formic acid according to the present invention not only has effects of reducing body weight and inhibiting fat accumulation in organs, but also has activity to effectively lower blood triglyceride and cholesterol levels, and therefore, the composition comprising the strain as an active ingredient can be favorably used as a composition capable of preventing/alleviating or treating obesity or metabolic syndromes caused by obesity. Therefore, the strain having excellent ability to produce formic acid according to the present invention can be favorably used as a material for a medical product or health food.

Abstract: Methods and compounds are disclosed for irreversibly inhibiting a DNA repair enzyme that possesses lyase activity.

Abstract: This invention relates to a stereochemically pure uracyl spirooxetane nucleoside phosphoramidate useful in the treatment of patients infected with the hepatitis C virus (HCV).

Abstract: Oligonucleotides with a novel sugar-phosphate backbone containing at least one 2?-arabino-fluoronucleoside and an internucleoside 3?-NH—P(—O)(OR)—O-5? linkage, where R is a positively charged counter ion or hydrogen, and methods of synthesizing and using the inventive oligonucleotides are provided. The inventive phosphoramidate 2?-arabino-fluorooligonucleotides have a high RNA binding affinity to complementary nucleic acids and are base and acid stable.

Abstract: The present invention relates to novel bisphosphonate duplex drugs, methods for preparing said compound; pharmaceutical compositions containing the same; as well as the use of said compounds in human and veterinary medicine, and, in particular, for treating tumors, viral infections; or dental disorders.

Abstract: Provided are compounds of Formula I: nucleosides, nucleoside phosphates and prodrugs thereof, wherein R6 is CN, ethenyl, 2-haloethen-1-yl, or (C2-C8)-alkyn-1-yl. The compounds, compositions, and methods provided are useful for the treatment of Flaviviridae virus infections.

Abstract: The present invention relates to methods for the labeling of nucleic acid polymers in vitro and in vivo. In particular, the methods include a [3+2] cycloaddition between a nucleotide analog incorporated into a nucleic acid polymer and a reagent attached to a label. Such methods do not require fixation and denaturation and therefore can be applied to the labeling of nucleic acid polymers in living cells and in organisms. Also provided are methods for measuring cellular proliferation. In these methods, the amount of label incorporated into the DNA is measured as an indication of cellular proliferation. The methods of the invention can be used in a wide variety of applications including clinical diagnosis of diseases and disorders in which cellular proliferation is involved, toxicity assays, and as a tool for the study of chromosomes' ultrastructures.

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

Abstract: Nucleic acid labeling compounds are disclosed. The compounds are synthesized by condensing a heterocyclic derivative with a cyclic group (e.g. a ribofuranose derivative). The labeling compounds are suitable for enzymatic attachment to a nucleic acid, either terminally or internally, to provide a mechanism of nucleic acid detection.

Abstract: Nucleosides and nucleotides are disclosed that are linked to detectable labels via a cleavable linker group.

Abstract: A tumor radiation probe of iodine-123 marker thymidine (FLT) analogue [123I]-IaraU is disclosed. Commercial available uridine is used as the raw material for the synthesis of the precursor. A radioactive iodine-123 is marked on an alkaline group of uridine to obtain [123I]-IaraU, which is distinguishable from [18F]-FLT marking 18F on a glycosyl group to obtain a novel tumor radiation probe. The marking procedures include mixing the marker precursor with Na [123I] solution, acetic acid and hydrogen peroxide solution, and the solution of chloroform and sodium hydroxide. The sonication time increases from 1 minute to 10 minutes, so that [123I]-IaraU has radiologically chemical purity of higher than 98% and radiological specific activity of not less than 0.196 GBq/umole, and the yield can increase from 8% to 40%. Its radioactive specific activity, yield and purity reach to the degree for the use in biological experiments, while reducing production cost.

Abstract: The present disclosure relates to photoactivable protecting groups containing a diarylsulfide chromophore, a method for the synthesis thereof and their use as photoactivable protecting groups using maskless photolithography based array synthesis.

Abstract: Compounds containing nucleic acid bases or their precursors modified by enrichment at specific sites with heavy stable isotopes of elements naturally present at those sites in minute amount are useful for the treatment of diseases characterized by altered gene expression and altered pattern of epigenomic control. These compounds, when used as nutrients or in other medicinal application methods, can alter the DNA methylation pattern in a simple way through the well-understood mechanism of kinetic isotope effect (KIE). This effect could also be useful for modifying methylation kinetics in stem cell technology, cloning and as disease therapeutics.

Abstract: Fluorinated pyrimidine analog compounds, compositions that include the fluorinated pyrimidine analog compounds, methods for making the fluorinated pyrimidine analog compounds, and methods for inhibiting DNA methyltransferase, treating solid tumors, and treating hematologic cancers by administering the fluorinated pyrimidine analog compounds.

Abstract: The present invention provides certain tetrahydrouridine derivative compounds, pharmaceutical compositions and kits comprising such compounds, and methods of making and using such compounds.

Abstract: Amphiphilic prodrugs of general formula A-X are disclosed, wherein A is a biologically active agent or may be metabolised to a biologically active agent; and X is selected from the group consisting of R, or up to three R moieties attached to a linker, Y1, Y2 or Y3, wherein R is selected from a group consisting of alkyl, alkenyl, alkynyl, branched alkyl, branched alkenyl, branched alkynyl, substituted alkyl, substituted alkenyl and substituted alkynyl groups and their analogues; Y1 is a linker group which covalently attached to an R group at one site and is attached to A at a further independent site; Y2 is a linker group which is covalently attached to two R groups at two independent sites and is attached to A at a further independent site; and Y3 is a linker group which is covalently attached to three R groups at three independent sites and is attached to A at a further independent site.

Abstract: An improved process for the preparation of (2?R)-2?-deoxy-2?-fluoro-2?-methylcytidine derivatives of formula I wherein R1 is selected from C1-4-alkyl is described. The (2?R)-2?-deoxy-2?-fluoro-2?-methylcytidine derivatives of formula I have the potential to be useful as prodrugs for potent inhibitors of the Hepatitis C Virus (HCV) NS5B polymerase.

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 present invention relates to the field of pharmacochemistry. Disclosed are fluorinated and azido-substituted pyrimidine nucleoside derivatives, and preparation methods and uses thereof. The structural formula is as shown (I). These compounds can be used for preparing medicaments for treating diseases such as tumors and viral infections, and can be used separately or in combination with other medicaments. The compounds also have effective activity against diseases such as tumors and viral infections, while having few side effects, and thus have potential application value.

Abstract: Compounds of formula I: including any possible stereoisomers thereof, wherein: R1 is hydrogen, —C(?O)R6 or —C(?O)CHR7—NH2; R2 is hydrogen; or C1-C6alkyl or phenyl, either of which is optionally substituted with 1, 2 or 3 substituents each independently selected from halo, C1-C6alkyl, C2-C6-alkenyl and C1-C6alkoxy, hydroxy or amino, or R2 is naphtyl; or R2 is indolyl, R3 is hydrogen, C1-C6alkyl, benzyl; R4 is hydrogen, C1-C6alkyl, benzyl; or R3 and R4 together with the carbon atom to which they are attached form C3-C7cycloalkyl; R5 is C1-C10alkyl, C3-C7-cycloalkyl, benzyl, or phenyl, any of which being optionally substituted with 1, 2 or 3 substituents each independently selected from hydroxy, C1-C6alkoxy, amino, mono- and diC1-C6alkylamino; R6 is C1-C6 alkyl; R7 is C1-C6 alkyl; R8 is hydrogen or halogen; or a pharmaceutically acceptable salt or solvate thereof are useful in the prophylaxis or treatment of HCV infections.

Abstract: The present invention relates to methods for the labeling of nucleic acid polymers in vitro and in vivo. Certain methods are provided that include a [3+2] cycloaddition between a nucleotide analogue incorporated into a nucleic acid polymer and a reagent attached to a label. Other methods are provided that include a Staudinger ligation between a nucleotide analogue incorporated into a nucleic acid polymer and a reagent comprising a substituted triarylphosphine attached to a label. Such methods do not require fixation and denaturation and therefore can be applied to the labeling of nucleic acid polymers in living cells and in organisms. Also provided are methods for measuring cellular proliferation. In these methods, the amount of label incorporated into the DNA is measured as an indication of cellular proliferation.

Abstract: Novel compounds and pharmaceutical compositions are provided. In one aspect of the invention the compounds may be utilized in medical practice, for example, in treatment of cancer and immune disorders.

Abstract: Embodiments are disclosed herein that involve C5-functionalized nucleic acids, which can be used for detecting a target in a nucleic acid. Particular embodiments disclose methods for making these compounds, wherein the compounds can be formed by coupling of an intermediate with a linker. Certain embodiments disclose the use of these compounds for detecting single nucleotide polymorphisms, and for increasing the thermal affinity of nucleic acid complements as compared to unmodified nucleic acid complements. In addition, the disclosed compounds can decrease enzymatic degradation of nucleic acids.

Abstract: The present invention relates to prodrug forms of ?-L-1-[5-(E-2-Bromovinyl)-2-(hydroxymethyl)-1,3-dioxolan-4-yl)]uracil (L-BHDU) and their use to treat viral infections of Varicella Zoster Virus, including recurrent VZV (shingles), especially including drug resistant Varicella Zoster Virus and related complications of this viral infection such as rash or post-herpetic neuralgia.

Abstract: Compounds of the formula I: including any possible stereoisomers thereof, wherein: R1 is hydrogen or halo; R4 is a monophosphate, diphosphate or triphosphate ester; or R4 is a group of formula R7 is optionally substituted phenyl; naphthyl; indolyl or N—C1-C6alkyloxycarbonyl-indolyl; R8 is hydrogen, C1-C6alkyl, benzyl; R8? is hydrogen, C1-C6alkyl, benzyl; or R8 and R8? together with the carbon atom to which they are attached form C3-C7cycloalkyl; R9 is C1-C10alkyl, benzyl, or optionally substituted phenyl; or a pharmaceutically acceptable salt or solvate thereof. pharmaceutical formulations and the use of compounds I as HCV inhibitors.

Abstract: An RNA of the present invention is an RNA containing a 5? cap structure and a coding region having a 5? initiation codon and a 3? stop codon on both ends of the coding region, the RNA having a nucleoside compound introduced at a site selected from among the 5? cap structure and 10 bases from a 5? end of the RNA, wherein the nucleoside compound is such that a group is attached to (i) a carbon atom at position 8 of a purine nucleus or (ii) a carbon atom at position 5 or 6 of a pyrimidine nucleus, the group being represented by formula (I): A-X?X-#??(I) where A represents an aryl group or a heteroaryl group, # represents a site where the group represented by the formula (I) is attached to the carbon atom at the position 8 of the purine nucleus or the carbon atom at the position 5 or 6 of the pyrimidine nucleus, and two Xs, which are identical to or different from each other, each represents a nitrogen atom or CH whose H may be substituted by alkyl.

Abstract: This disclosure provides novel reversibly terminated ribonucleotides which can be used as a reagent for DNA sequencing reactions. Methods of sequencing nucleic acids using the disclosed nucleotides are also provided.

Abstract: Disclosed is a stable crystal of 1-(2?-cyano-2?-deoxy-?-D-arabinofuranosyl)cytosine monohydrochloride. There is provided a crystal of 1-(2?-cyano-2?-deoxy-?-D-arabinofuranosyl)cytosine monohydrochloride having characteristic peaks at 13.7°, 15.7°, 16.0°, 18.6°, 20.3°, and 22.7° as diffraction angles (2?±0.1°) measured by powder X-ray diffraction, and having a melting point of 192° C. to 197° C.

Abstract: A method and composition for treating a host infected with hepatitis C comprising administering an effective hepatitis C treatment amount of a described 1?, 2? or 3?-modified nucleoside or a pharmaceutically acceptable salt or prodrug thereof, is provided.

Abstract: The present invention provides certain tetrahydrouridine derivative compounds, pharmaceutical compositions and kits comprising such compounds, and methods of making and using such compounds.

Abstract: Aspects of the invention include 2? protected nucleoside monomers that are protected at the 2? site with orthoester-type protecting groups. The 2? protected monomers also include a second, aryl carbonate-type, protecting group. Aspects of the invention further include nucleic acids that include the protecting groups of the invention, as well as methods of synthesizing nucleic acids using the protecting groups of the invention.

Abstract: The present invention relates to novel compounds according to the general formulas I, II, III, IV or V: wherein B is nucleoside base according to the structure: and the remaining variables as defined in the specification, and pharmaceutical compositions comprising the compounds. The compounds are useful interalia as anti-viral agents in viral therapy.

Abstract: A di(pyrimidine nucleoside 5?-)polyphosphate is synthesized by converting a pyrimidine nucleoside 5?-triphosphate into a pyrimidine nucleoside 5?-cyclic triphosphate by use of a condensing agent, and subsequently reacting the pyrimidine nucleoside 5?-cyclic triphosphate with a pyrimidine nucleotide in the presence of a salt of a metal selected from among magnesium, manganese, and iron. Through the method of the invention, a di(pyrimidine nucleoside 5?-)polyphosphate can be synthesized from an unprotected pyrimidine nucleoside 5?-phosphate serving as a starting material at a synthesis yield of 50% or higher. Therefore, the method of the invention is suitable for large-scale synthesis of a di(pyrimidine nucleoside 5?-)polyphosphate.

Abstract: This disclosure provides novel reversibly terminated ribonucleotides which can be used as a reagent for DNA sequencing reactions. Methods of sequencing nucleic acids using the disclosed nucleotides are also provided.

Abstract: Disclosed herein are novel phosphonate nucleosides and thiophosphonate nucleosides comprising a phosphonalkoxy-substituted or phosphonothioalkyl-substituted five-membered, saturated or unsaturated, oxygen-containing or sulfur-containing ring coupled to a heterocyclic nucleobase such as a pyrimidine or purine base. The invention further relates to compounds having HIV (Human Immunodeficiency Virus) replication inhibiting properties and to compounds having antiviral activities with respect to other viruses. The invention also relates to methods for preparation of all such compounds and pharmaceutical compositions comprising them. The invention further relates to the use of said compounds as a medicine and in the manufacture of a medicament useful for the treatment of subjects suffering from HIV infection, as well as for treatment of other viral, retroviral or lentiviral infections and to the treatment of animals suffering from FIV, viral, retroviral or lentiviral infections.

Abstract: The invention relates to the use of 1-(?-D-Ribofuranosyl)-1,2-dihydropyrimidin-2-one derivative or mimetic or an analogue, derivatives, metabolites, variants or salts thereof for the manufacturing of a medicament to increase the amount of Indoleamine 2,3-dioxygenase (IDO) production in order to induce immunological tolerance as well as a method of treating a mammal in need thereof.

Abstract: Novel compounds and pharmaceutical compositions are provided. In one aspect of the invention the compounds may be utilized in medical practice, for example, in treatment of cancer and immune disorders.

Abstract: Described herein are compounds useful in the modulation of blood uric acid levels, formulations containing them and methods of using them. In some embodiments, the compounds described herein are used in the treatment or prevention of disorders related to aberrant levels of uric acid.

Abstract: To provide a compound which exhibits excellent anti-tumor activity and excellent oral absorption and which is a useful anti-tumor drug. The invention provides a 3?-ethynylcytidine derivative represented by formula (1): (wherein X represents a (substituted) alkylcarbonyl group, a (substituted) alkoxycarbonyl group, or a hydrogen atom; one of Y and Z represents a hydrogen atom or a group represented by (R1)(R2)(R3)Si— and the other represents a group represented by (R4)(R5)(R6)Si—; and R1, R2, R3, R4, R5, and R6 each represent a (substituted) alkyl group, a (substituted) cyclic alkyl group, or a (substituted) aryl group) or a salt thereof.

Abstract: Hydrazino, oxyamino and carbonyl-based monomers and methods for incorporation into oligonucleotides during enzymatic synthesis are provided. Modified oligonucleotides are provided that incorporate the monomers provided herein. Immobilized oligonucleotides and oligonucleotide conjugates that contain covalent hydrazone or oxime linkages are provided. Methods for preparation of surface bound oligonucleotides are provided. Methods for the preparation of oligonucleotide conjugates are also provided.

Abstract: Oligonucleotides with a novel sugar-phosphate backbone containing at least one 2?-arabino-fluoronucleoside and an internucleoside 3?-NH—P(?O)(OR)—O-5? linkage, where R is a positively charged counter ion or hydrogen, and methods of synthesizing and using the inventive oligonucleotides are provided. The inventive phosphoramidate 2?-arabino-fluorooligonucleotides have a high RNA binding affinity to complementary nucleic acids and are base and acid stable.

Abstract: Disclosed herein are phosphoramidate prodrugs of nucleoside derivatives for the treatment of viral infections in mammals, which is a compound, its stereoisomer, salt (acid or basic addition salt), hydrate, solvate, or crystalline form thereof, represented by the following structure: Also disclosed are methods of treatment, uses, and processes for preparing each of which utilize the compound represented by formula I.

Abstract: 4-Amino-1-((2R,3S,4S,5R)-5-azido-4-hydroxy-5-hydroxymethyl-3-methyl-tetrahydro-furan-2-yl)-1H-pyrimidin-2-one (22) and prodrugs thereof are hepatitis C (HCV) polymerase inhibitors. Also disclosed are compositions and methods for inhibiting HCV and treating HCV-mediated diseases, processes for making the compounds and synthetic intermediates employed in the process.

Abstract: The present invention provides a method for detecting methylcytosine in DNA rapidly, conveniently, and with high sensitivity. The present invention relates to a method for detecting methylcytosine by using a methylcytosine photocoupling agent (a photoresponsive probe) consisting of nucleic acids having a group represented by the Formula (I), (II), (III) or (IV) as a base moiety.

Abstract: Compounds containing nucleic acid bases or their precursors modified by enrichment at specific sites with heavy stable isotopes of elements naturally present at those sites in minute amount are useful for the treatment of diseases characterized by altered gene expression and altered pattern of epigenomic control. These compounds, when used as nutrients or in other medicinal application methods, can alter the DNA methylation pattern in a simple way through the well-understood mechanism of kinetic isotope effect (KIE). This effect could also be useful for modifying methylation kinetics in stem cell technology, cloning and as disease therapeutics.

Abstract: Nucleic acid labeling compounds are disclosed. The compounds are synthesized by condensing a heterocyclic derivative with a cyclic group (e.g. a ribofuranose derivative). The labeling compounds are suitable for enzymatic attachment to a nucleic acid, either terminally or internally, to provide a mechanism of nucleic acid detection.

Abstract: Processes for the preparation of racemic and optically active nucleoside analogs of formula (A) are described. These compounds are useful as anti-infective agents, antisense therapeutic agents and hybridization assay probes.

Abstract: An oligo- or polynucleotide analogue having one or more structures of the general formula where B is a pyrimidine or purine nucleic acid base, or an analogue thereof, is disclosed. The use of this analogue provides an oligonucleotide analogue antisense molecule, which is minimally hydrolyzable with an enzyme in vivo, has a high sense strand binding ability, and is easily synthesized.