Abstract: The invention relates to a method of treating a mitochondrial DNA depletion syndrome, comprising administering to a patient a therapeutically-effective amount of a compound of formula (I) or a pharmaceutically acceptable salt thereof.

Abstract: Nicotinamide ribose has many applications, including as a dietary supplement. This invention convers a process to prepare nicotinamide ribose it in its phosphorylated form. The instant invention is based on the discovery that nicotinamide ribose phosphate emerges in stable form by direct reaction of ribose-1,2-cyclic phosphate. It is based on the further conversion of the phosphorylated nicotinamide ribose product to unphosphorylated nicotinamide ribose upon treatment with an enzymatic phosphatase, most preferably in buffer containing borate. It is based on the further discovery that compositions of nicotinamide ribose with borate slow the decomposition of nicotinamide ribose, and therefore is more useful than compositions of nicotinamide ribose without borate.

Abstract: Disclosed herein are methods of preparing a nucleoside analog, Compound (I): or a pharmaceutically acceptable salt thereof, which is useful in treating diseases and/or conditions such as viral infections, and intermediates thereof.

Abstract: Provided herein are bridged cyclic phosphates and phosphoramidates (bc-ProTides) of nucleosides, which is a compound, its stereoisomers, isotope-enriched analogs, pharmaceutically acceptable salts, hydrates, solvates, or crystalline or polymorphic forms thereof, with the following structure: These compounds can be used for the treatment of viral infections and/or neoplastic diseases in mammals. By optimizing combinations of Y2, Y3, R0, and M, the cleavability of these compounds as prodrugs can be attuned for different tissue targeting with various functional combinations. Also disclosed are processes and methods for preparation of these compounds.

Abstract: Disclosed herein are phosphorothioate nucleotide analogs, methods of synthesizing phosphorothioate nucleotide analogs and methods of treating diseases and/or conditions such as viral infections, cancer, and/or parasitic diseases with the phosphorothioate nucleotide analogs.

Abstract: The present invention provides novel tricyclic nucleosides and oligomeric compounds prepared therefrom. Incorporation of one or more of the tricyclic nucleosides into an oligomeric compound is expected to enhance one or more properties of the oligomeric compound. Such oligomeric compounds can also be included in double stranded compositions. In certain embodiments, the oligomeric compounds provided herein are expected to hybridize to a portion of a target RNA resulting in loss of normal function of the target RNA.

Abstract: Provided herein are novel bicyclic nucleosides, oligomeric compounds that include such bicyclic nucleosides and methods of using the oligomeric compounds. More particularly, the novel bicyclic nucleosides comprise a furanose ring system having a bridge comprising a 4?-methylene group attached to a 2?-sulfoxide or sulfone group and optionally including one or more substituent groups attached to the 4?-methylene and or the 5?-position. In certain embodiments, the oligomeric compounds provided herein are expected to hybridize to a portion of a target RNA resulting in loss of normal function of the target RNA.

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

Abstract: The present invention provides modified nucleosides and oligomeric compounds prepared therefrom. More particularly, the present invention provides modified nucleosides having at least one 5?-substituent and a 2?-O-substituent, oligomeric compounds comprising at least one of these modified nucleosides and methods of using the oligomeric compounds. In some embodiments, the oligomeric compounds provided herein are expected to hybridize to a portion of a target RNA resulting in loss of normal function of the target RNA.

Abstract: The present invention relates to compounds and their use in competitive protein binding assays, for example for use with glycosyl transferase and/or glycoprocessing proteins. The present application also provides kits and apparatuses for use in the assays. In particular, the present invention provides a compound of the formula (I): wherein n is 1, 2 or 3; R1 is selected from —OH, —OPO3H, —OR4, —NHR4, R6; R2 and R3 are each independently selected from —H, —OH, optionally substituted —O-alkyl and —O-alkanoyl; R4 is selected from an optionally substituted mono or polysaccharide, -alkyl, -alkenyl, -alkynyl, and L-Z, where L is a linking agent and Z is a binding agent; R6 is an optionally substituted hydrocarbon group; A is either (i) a substituted heteroaryl group, the substituent on the heteroaryl group having a double bond conjugated to the heteroaryl group, or (ii) a substituted aryl group, the substituent on the aryl group having a double bond conjugated to the aryl group.

Abstract: This invention relates to antisense oligonucleotides comprising at least one N3??P5? phosphorodiamidate linkage (NPN) in the backbone as well as methods for using the same. The antisense oligonucleotides can effectively prevent or decrease protein expression.

Abstract: The present invention provides bicyclic cyclohexose nucleoside analogs and oligomeric compounds comprising these nucleoside analogs. These bicyclic nucleoside analogs are useful for enhancing properties of oligomeric compounds including nuclease resistance.

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: Disclosed herein are nucleosides, nucleotides and nucleotide analogs, methods of synthesizing the same and methods of treating diseases and/or conditions such as a Picornavirus and/or Flaviviridae infection with one or more nucleosides, nucleotides and nucleotide analogs.

Abstract: This invention relates to a stereochemically pure uracyl spirooxetane nucleoside phosphoramidate which inhibits the hepatitis C virus (HCV).

Abstract: Synthesis and uses of conformationally restricted nucleomonomers (CRN) to prepare nucleic acid compounds. Methods for preparing nucleomonomers for nucleic acid compounds in high yields and in multi-gram scale for therapeutic modalities useful for treating or preventing diseases or disorders by up- or down-regulating the expression of genes and other nucleic acid based regulatory systems in a cell.

Abstract: Disclosed herein are phosphorothioate nucleotide analogs, such as thiophosphoroamidate prodrugs and thiophosphates (including ?-thiomonophosphates, ?-thiodiphosphates, and ?-thiotriphosphates), methods of synthesizing phosphorothioate nucleotide analogs, such as thiophosphoramidate prodrugs, and thiophosphates and methods of treating viral infections, such as HCV, cancer, and/or parasitic diseases with the phosphorothioate nucleotide analogs, such as thiophosphoramidate prodrugs, and thiophosphates.

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 provides nucleosides of formula (1) and oligonucleotides comprising at least one nucleoside of formula (2): Another aspect of the invention relates to a method of inhibiting the expression of a gene in cell, the method comprising (a) contacting an oligonucleotide of the invention with the cell; and (b) maintaining the cell from step (a) for a time sufficient to obtain degradation of the mRNA of the target gene.

Abstract: Disclosed herein are phosphorothioate nucleotide analogs, methods of synthesizing phosphorothioate nucleotide analogs and methods of treating diseases and/or conditions such as viral infections, cancer, and/or parasitic diseases with the phosphorothioate nucleotide analogs.

Abstract: Orthogonally protected 3?-amino nucleoside monomers and efficient methods for their synthesis are described. The methods employ selective protection of the 3?-amino group in the presence of the unprotected nucleoside base.

Abstract: To provide an anti-cancer agent sensitivity determination marker, which marker can determine whether or not the patient has a therapeutic response to the anti-cancer agent, and novel cancer therapeutic means employing the marker. The anti-cancer agent sensitivity determination marker, the anti-cancer agent including oxaliplatin or a salt thereof and fluorouracil or a salt thereof, contains one or more substances selected from among an amino-acid-metabolism-related substance, a nucleic-acid-metabolism-related substance, a substance in the pentose phosphate pathway, a substance in the glycolytic pathway, a substance in the TCA cycle, a polyamine-metabolism-related substance, 7,8-dihydrobiopterin, 6-phosphogluconic acid, butyric acid, triethanolamine, 1-methylnicotinamide, NADH, NAD+, and a substance involved in the metabolism of any of these substances.

Abstract: The present invention describes Photolabile Compounds methods for use of the compounds. The Photolabile Compounds have a photoreleasable ligand, which can be biologically active, and which is photoreleased from the compound upon exposure to light. In some embodiments, the Photolabile Compounds comprise a light antenna, such as a labeling molecule or an active derivative thereof. In one embodiment, the light is visible light, which is not detrimental to the viability of biological samples, such as cells and tissues, in which the released organic molecule is bioactive and can have a therapeutic effect. In another embodiment, the photoreleasable ligand can be a labeling molecule, such as a fluorescent molecule.

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: Phosphoramidate derivatives of 5-fluoro-2?-deoxyuridine are disclosed for use in the treatment of cancer, especially in the treatment of cancer where the patient shows resistance, for example, in a patient with cells with a lowered level of nucleoside transporter proteins and/or with nucleoside kinase-deficient cells and/or with mycoplasma-infected cells and/or with cells with a raised level of thymidylate synthase.

Abstract: Compounds of the formula I: including any possible stereoisomers thereof, wherein: R4 is a monophosphate, diphosphate or triphosphate ester; or R4 is R7 is optionally substituted phenyl, optionally substituted naphthyl, or optionally substituted indolyl; R8 and R8? are hydrogen, C1-C6alkyl, benzyl, or phenyl; or R8 and R8? form C3-C7cycloalkyl; R9 is C1-C10alkyl, C3-C7cycloalkyl, phenyl or phenyl-C1-C6alkyl, wherein the phenyl moiety in phenyl or phenyl-C1-C6alkyl is optionally substituted; or a pharmaceutically acceptable salt or solvate thereof; pharmaceutical formulations and the use of compounds I as HCV inhibitors.

Abstract: The invention provides methods and compositions for the rapid and sensitive detection of post-translationally modified proteins, and particularly of those with posttranslational glycosylations. The methods can be used to detect O-GlcNAc posttranslational modifications on proteins on which such modifications were undetectable using other techniques. In one embodiment, the method exploits the ability of an engine˜red mutant of ?-1,4-galactosyltransferase to selectively transfer an unnatural ketone functionality onto O-GlcNAc glycosylated proteins. Once transferred, the ketone moiety serves as a versatile handle for the attachment of biotin, thereby enabling detection of the modified protein. The approach permits the rapid visualization of proteins that are at the limits of detection using traditional methods. Further, the preferred embodiments can be used for detection of certain disease states, such as cancer, Alzheimer's disease, neurodegeneration, cardiovascular disease, and diabetes.

Abstract: Disclosed herein are nucleosides, nucleotides and analogs thereof, pharmaceutical compositions that include one or more of nucleosides, nucleotides and analogs thereof, and methods of synthesizing the same. Also disclosed herein are methods of ameliorating and/or treating a paramyxovirus viral infection, with a nucleoside, a nucleotide and an analog thereof.

Abstract: The present disclosure relates to compounds of Formula (I): Also disclosed are pharmaceutical compositions comprising compounds of Formula (I), methods of using the compounds of Formula (I) and/or compositions comprising the compounds of Formula (I) for the treatment of HCV.

Abstract: The present invention relates to the use of nucleoside derivatives of formula (I) wherein the symbols are as the specification, and of pharmaceutically acceptable salts thereof and to pharmaceutical compositions containing such compounds.

Abstract: The invention provides small molecule drugs that are chemically modified by covalent attachment of a water soluble, non-peptidic oligomer. The conjugates of the invention, when administered by any of a number administration routes, exhibits advantages over previously administered compounds.

Abstract: The present invention is directed to n-alkylated synthetic nucleosides of high regiospecific purity and oligonucleotides that can be utilized for studies on reversal of cytotoxic and mutagenic DNA damage, and as diagnostic tools.

Abstract: The present disclosure relates to the compound of Formula I: Also disclosed are pharmaceutical compositions comprising the compound of Formula I, methods of using the compound of Formula I and/or compositions comprising the compound of Formula I for the treatment of HCV.

Abstract: The present disclosure relates to the compound of Formula I: Also disclosed are pharmaceutical compositions comprising the compound of Formula I, methods of using the compound of Formula I and/or compositions comprising the compound of Formula I for the treatment of HCV.

Abstract: Disclosed herein are a composition and unit dosage form for the treatment of hepatitis C virus (HCV) infection comprising GS-7977 and at least one pharmaceutically acceptable excipient, as well as methods for making said composition and unit dosage form. Also disclosed herein is a method of treating a subject, preferably a human, infected with hepatitis C virus, said method comprising administering to the subject for a time period an effective amount of GS-7977 and an effective amount of ribavirin. In one aspect, the method comprises administering to the subject an interferon-free treatment regimen comprising an effective amount of GS-7977 and an effective amount of ribavirin. In a particular aspect, the method is sufficient to produce an undetectable amount of HCV RNA in the subject for at least 12 weeks after the end of the time period.

Abstract: Provided herein are compounds, compositions, and methods of using them to treat infections, neoplastic disease, inflammatory disease, and pain. Such compounds are nucleotides, acyclonucleotides, and ANP phosphonates conjugated with forms and/or moieties of Vitamin B6 for delivery past the cell membrane and into the cell.

Abstract: Disclosed herein are nucleosides, nucleotides and analogs thereof, pharmaceutical compositions that include one or more of nucleosides, nucleotides and analogs thereof, and methods of synthesizing the same. Also disclosed herein are methods of ameliorating and/or treating a disease and/or a condition, including an infection from a paramyxovirus and/or an orthomyxovirus, with a nucleoside, a nucleotide and an analog thereof. Examples of viral infections include a respiratory syncytial viral (RSV) and influenza infection.

Abstract: The present disclosure relates to new polymethine compounds and their use as fluorescent labels. The compounds may be used as fluorescent labels for nucleotides in nucleic acid sequencing applications.

Abstract: Disclosed herein are phosphorothioate nucleotide analogs, such as thiophosphoroamidate prodrugs and thiophosphates (including ?-thiomonophosphates, ?-thiodiphosphates, and ?-thiotriphosphates), methods of synthesizing phosphorothioate nucleotide analogs, such as thiophosphoramidate prodrugs, and thiophosphates and methods of treating viral infections, such as HCV, cancer, and/or parasitic diseases with the phosphorothioate nucleotide analogs, such as thiophosphoramidate prodrugs, and thiophosphates.

Abstract: The invention is directed to processes of preparing phosphonate nucleosides comprising a phosphonalkoxy-substituted five-membered, saturated or unsaturated, oxygen-containing ring coupled to a heterocyclic nucleobase such as a pyrimidine or purine base.

Abstract: Provided herein are compounds, compositions, and methods of using them to treat infections, neoplastic disease, inflammatory disease, and pain. Such compounds are nucleotides, acyclonucleotides, and ANP phosphonates conjugated with forms and/or moieties of Vitamin B6 for delivery past the cell membrane and into the cell.

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: The present invention relates to the novel diastereoselective syntheses for generating phosphorothioate compounds. Examples include nucleoside phosphorothioate analogs that are useful in treating diseases and/or conditions such as viral infections.

Abstract: Deuterated nucleoside analogs of Formula (I) and the pharmaceutically acceptable salts thereof are provided by this disclosure The variables, e.g., B1, Y, R1, R2, R3, R3?, R4, R5, R6, R7, R8, and R9 carry definitions set forth in the disclosure. Compounds of Formula (I) are deuterated at one or more positions and the deuterium enrichment at each deuterated positions is at least 50%. Compounds and salts of Formula (I) are useful for treating viral infections, including HCV infections.

Abstract: The invention relates to a method for preparing nanoparticles based on functional amphiphilic molecules or macromolecules, optionally in the presence of at least one colipide, enabling the encapsulation of therapeutic agents, especially anti-tumoral agents, and the use thereof for the transport and vectorization of therapeutic agents, especially anti-tumoral agents.

Abstract: A deuterated nucleoside analog of the formula and the pharmaceutically acceptable salts thereof are provided by this disclosure. The disclosure also includes pharmaceutical compositions comprising a compound or salt of the formula and a carrier. Compounds and salts of this formula are useful for treating viral infections, including HCV infections. A method for treating a host afflicted with hepatitis C or other disorders is also presented that includes administering an effective treatment amount of a nucleoside or nucleotide that has deuterium with at least 50% enrichment at the 5?-position of the nucleoside or nucleotide.

Abstract: This invention is directed to compounds of Formula (I) having the structure that are useful in the treatment of viral infections in mammals, particularly in humans, mediated, at least in part, by a virus in the Flaviviridae family of viruses.

Abstract: The invention provides methods of removing contaminants from a mixture of a desired product and contaminants by pH adjustments and molecular weight cut-offs. The contaminants include phosphate groups, magnesium sulfate, sodium pyruvate and tetrasodium pyrophosphate groups. The desired product includes nucleotide sugars, glycolipids, LnNT, sialyl lactose, and salts.

Abstract: Provided herein are compounds, compositions and methods for the treatment of Flaviviridae infections, including HCV infections. In certain embodiments, compounds and compositions of nucleoside derivatives are disclosed, which can be administered either alone or in combination with other anti-viral agents. In certain embodiments, the compounds are 2?-cyano, azido or amino nucleosides according to Formula 1001 or 2001: or a pharmaceutically acceptable salt, solvate, stereoisomeric form, tautomeric form, or polymorphic form thereof, wherein Base, W, R1 and R2 are as described herein.

Abstract: Phosphoramidate derivatives of nucleotides and their use in the treatment of cancer are described. The base moieties of, for example, each of deoxyuridine, cytarabine, gemcitabine and citidine may be substituted at the 5-position. The phosphoramidate moiety has attached to the P atom an aryl-O moiety and an ?-amino acid moiety. The ?-amino acid moiety may correspond to or be derived from either a naturally occurring or a non-naturally occurring amino acid.