Abstract: The invention relates to a method for producing phosphate-bridged nucleoside conjugates. In the method a nucleophile is first dissolved in a non-aqueous solvent and dried, and a cyclosaligenyl phosphate compound is subsequently added to the solution.

Abstract: Compounds, compositions, and methods for optical, including fluorescence optical, determinations useful in labeling biomolecules such as protein and deoxyribonucleic acid for their detection and quantitation. The compounds are diastereomeric cyanines with high hydrophilicity and other desirable properties.

Abstract: This invention provides for labeling reagents, labeled targets and processes for preparing labeling reagents. The labeling reagents can take the form of cyanine dyes, xanthene dyes, porphyrin dyes, coumarin dyes or composite dyes. These labeling reagents are useful for labeling probes or targets, including nucleic acids and proteins. These reagents can be usefully applied to protein and nucleic acid probe based assays. They are also applicable to real-time detection processes.

Abstract: Aortic valve stenosis (AS) is a chronic process related to a progressive mineralization of the aortic root and valve cusps. We found in human AS valves a high level of expression and enzymatic activity of ectonucleotide pyrophosphatase/phosphodiesterase-1 (ENPP-1), which correlated to the degree of mineralization. In vitro, inhibition of ENPP activity with ARL 67156 significantly reduced calcification of isolated valve interstitial cells. In a rat model of cardiovascular calcification, ARL 67156 significantly reduced calcification of the aortic root and valve cusps. This is the first study to demonstrate that increased expression and activity of ENPP-1 promotes the mineralization process in AS valves. Hence, inhibition of ectonucleotidase may represent a novel target of therapy for this frequent and serious cardiovascular disease.

Abstract: The object of the present invention is to provide a nucleoside or a nucleotide, or a derivative thereof, which has an unnatural base. The nucleoside and others of the present invention are characterized by having a 2-amino-6-(2-thiazolyl)purin-9-yl group or a 2-amino-6-(2-oxazolyl)purin-9-yl group as a base, wherein the 4- and/or 5-position of the thiazolyl or oxazolyl group may be substituted.

Abstract: The invention generally relates to nucleotide analogs and methods of their use in sequencing-by-synthesis reactions. In certain embodiments, the invention provides a nucleotide analog including a detectable label attached to a nitrogenous base portion of a nucleotide analog by a cleavable linker, in which contact of the analog with at least one activating agent results in cleavage of the label and elimination of the linker, thereby producing a natural nucleotide, a 9-deaza-G, 9-deaza-A, or ?-uridine.

Abstract: The present invention relates to the use of nucleoside derivatives of formula Ia wherein the symbols are as defined in the specification, and of pharmaceutically acceptable salts thereof which inhibit HCV polymerase and are useful for treating a patient suffering from a HCV infection and to pharmaceutical compositions containing such compounds.

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: This invention provides a process for sequencing nucleic acids using 3? modified deoxynucleotide analogues or 3? modified deoxyinosine triphosphate analogues, and 3? modified dideoxynucleotide analogues having a detectable marker attached to a base thereof.

Abstract: The invention is directed to modified guanine-containing nucleosides and nucleotides and uses thereof. More specifically, the invention relates to modified fluorescently labelled guanine-containing nucleosides and nucleotides which exhibit enhanced fluorophore intensity by virtue of reduced quenching effects.

Abstract: This invention provides novel azido linkers for deoxynucleotide analogues having a detectable marker attached thereto.

Abstract: This invention relates to certain chirally-correct mitoprotectant phosphorylated heterocyclic agents [formula (I)], which are useful for the treatment of dermatological disorders that include challenged skin from cancer, diabetes, radiation treatments, chemotherapy, and sun-burn; mitochondrial dysfunction; age spots; acne, loss of cellular antioxidants; skin changes associated with aging including collagen loss, loss of skin pliability, loss of skin suppleness, skin wrinkles and fine lines, oxidation, damage from radiation, damage from free radicals, and damage from UV; dry skin; xerosis; ichthyosis; dandruff; brownish spots; keratoses; melasma; lentigines; liver spots; skin pigmentation including pigmented spots, dark circles under the eyes, darkened skin, and blemishes; oily skin; warts; eczema; pruritic skin; psoriasis; inflammatory dermatoses; topical inflammation; disturbed keratinization; scalp dryness; skin depigmentation, and combinations thereof;

Abstract: Methods, apparatus, systems, computer programs and computing devices related to biologically assembling and/or synthesizing peptides and/or proteins are disclosed.

Abstract: The invention relates to analogous compounds of 6-thioguanosine triphosphate of general formula (I). A compound of the general formula (I); wherein the dashed bond in the sugar moiety can be either single or double and wherein R1, R2, R3, R4 or R5, equal or different between each other, have general formula -(Int)m-Ter, wherein m is between 0 and 12 and Int and Ter are Internal and Terminal building blocks, wherein Int is selected from the group consisting of formula (II); and Ter is selected from the group consisting of formula (III).

Abstract: 2? and/or 3? prodrugs of 1?, 2?, 3? or 4?-branched nucleosides, and their pharmaceutically acceptable salts and derivatives are described. These prodrugs are useful in the prevention and treatment of Flaviviridae infections, including HCV infection, and other related conditions. Compounds and compositions of the prodrugs of the present invention are described. Methods and uses are also provided that include the administration of an effective amount of the prodrugs of the present invention, or their pharmaceutically acceptable salts or derivatives. These drugs may optionally be administered in combination or alteration with further anti-viral agents to prevent or treat Flaviviridae infections and other related conditions.

Abstract: Nucleosides and nucleotides containing a tricyclic base portion thereof are useful for treating infectious diseases and proliferative disorders, such as viral infections or cancer respectively.

Abstract: Novel methods for enzymatic synthesis of nucleic acid chains and the substrates for the same are disclosed. The methods are based on a step-wise enzymatic reaction. The sequencing of nucleic acids is an example of the use of the claimed methods.

Abstract: Provided are nucleotide-dye conjugates and related compounds in which a dye is linked to a nucleobase directly or indirectly by an anionic linker. The anionic character of the linker is provided by one or more anionic moieties which are present in the linker, such as phosphate, phosphonate, sulfonate, and carboxylate groups. When the dye is a provided as a donor/acceptor dye pair, the anionic linker can be located between the donor and the acceptor, or between the nucleobase and either the donor or acceptor, or both. In one embodiment, conjugates of the invention provide enhanced electrophoretic mobility characteristics to sequencing fragments, e.g., for dideoxy sequencing using labeled terminators.

Abstract: Nucleotide analogues comprising a reactive hydrazide function (formula II) used as initial synthons for preparing compounds (formula I) capable of inducing mutations or capable of inhibiting a DNA polymerase or a kinase provided. Nucleic acids comprising the nucleotide and nucleoside analogues are also provided. Methods of using the compounds are also provided.

Abstract: Disclosed are cyanine dyes that are useful for labelling and detecting biological and other materials. The dyes are of formula (I): in which groups R3 and R4 are attached to the Z1 ring structure and groups R5 and R6 are attached to the Z2 ring structure, and n=1, 2 or 3; Z1 and Z2 independently represent the carbon atoms necessary to complete a one ring, or two-fused ring aromatic system; at least one of groups R1, R2, R3, R4, R5, R6 and R7 is the group -E-F where E is a single bond or a spacer group and F is a target bonding group; one or more of groups R11, R12, R13 and R14 are independently selected from the group —(CH2)k—W, where W is sulphonic acid or phosphonic acid and k is an integer from 1 to 10.

Abstract: Methods, apparatus, systems, computer programs and computing devices related to biologically assembling and/or synthesizing peptides and/or proteins are disclosed.

Abstract: Methods, apparatus, systems, computer programs and computing devices related to biologically assembling and/or synthesizing peptides and/or proteins are disclosed.

Abstract: The present invention provides dyes, reactive dyes and labeled reagents that may be used in the detection or quantification of desirable target molecules, such as proteins and nucleic acids. Dyes are provided that may be used free in solution where the binding of the dye to the target molecule provides signal generation. Dyes are also provided that comprise reactive groups that may be used to attach the dyes to probes that will bind to desirable target molecules. The novel dyes of the present invention have been modified by the addition of charged and polar groups to provide beneficial properties.

Abstract: The disclosure provides nucleotide analogs and methods of their use. Analogs of the invention comprise a reporter molecule (label) attached via the N4, N6, O4, or O6 position of the nitrogenous base portion of the analog. In a preferred embodiment, nucleotide analogs of the invention comprise a label attached to the nitrogenous base portion of the analog via a cleavable linker at the N4, O4, N6 or O6 position.

Abstract: A method for increasing oxytocin release through direct action on the epidermal keratinocytes is provided. The method for increasing oxytocin release in the epidermis includes increasing the calcium ion concentration in the epidermal cells. In the method of the present invention, the increase of the calcium ion concentration in the epidermal cells may be achieved by physically stimulating the skin. The physical stimulation may be achieved by applying a heat stimulus and/or a massage. The increase of the calcium ion concentration in the epidermal cells may be achieved by stimulating the epidermal cells by at least one agent selected from the group consisting of ATP, UTP, 4 alpha-phorbol 12,13-didecanoate, and pharmaceutically acceptable salts thereof.

Abstract: Nucelosides and nucleotides containing a tricyclic base portion thereof are useful for treating infectious diseases and proliferative disorders, such as viral infections or cancer respectively.

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: Disclosed are polycyclic polyether compounds of formula I and pharmaceutical compositions comprising such compounds. wherein R, OR1, and R2 are as defined herein. Also disclosed are methods of regulating mucus clearance in a cell, and methods of treating decreased mucus clearance or mucociliary dysfunction.

Abstract: The invention provides nucleoside and nucleotide molecules containing cleavable linkers linking a label such as a dye. The invention also provides nucleosides and nucleotide molecules containing a blocking group, either removable or non-removable. The invention additionally provides methods of using the nucleoside and nucleotide molecules containing a cleavable linker and/or a blocking group.

Abstract: Compounds, compositions, and methods for optical, including fluorescence optical, determinations useful in labeling biomolecules such as protein and deoxyribonucleic acid for their detection and quantitation. The compounds are diastereomeric cyanines with high hydrophilicity and other desirable properties.

Abstract: The disclosure encompasses caged compounds such as caged nucleoside phosphoesters (caged nucleotides). In an embodiment, the caged nucleotides include compounds corresponding to those described by formula (I) that may be activated by two-photon excitation, and methods of synthesis of such compounds. 8-Bromo-7-hydroxyquinoline-caged ATP was synthesized and examined for its photochemistry as a biologically useful, temporally and spatially controlled ATP-releasing reagent. The combination of two-photon excitation hydrolysis and activation of caged ATP enables methods for finely focusing ATP activation at the sub-cellular level or to a greater depth of activation, thereby providing improved resolution of ATP-dependent processes at the cellular level.

Abstract: The present invention relates generally to labeled and unlabled cleavable terminating groups and methods for DNA sequencing and other types of DNA analysis. More particularly, the invention relates in part to nucleotides and nucleosides with chemically cleavable, photocleavable, enzymatically cleavable, or non-photocleavable groups and methods for their use in DNA sequencing and its application in biomedical research.

Abstract: The present invention relates to methods of treating viral disease using mutagenic nucleoside analogs. In particular, the invention provides isoguanosine nucleosides and derivatives thereof as well a method of increasing the mutation rate of a virus such as bovine viral diarrhea virus (BVDV) and hepatitis C virus (HCV).

Abstract: Provided are imidazo[1,5-f][1,2,4]triazinyl, imidazo[1,2-f][1,2,4]triazinyl, and [1,2,4]triazolo[4,3-f][1,2,4]triazinyl nucleosides, nucleoside phosphates and prodrugs thereof. The compounds, compositions, and methods provided are useful for the treatment of Flaviviridae virus infections, particularly hepatitis C infections.

Abstract: Disclosed are methods for treating hepatitis C viral infections using deaza-purine compounds of Formula I: wherein W, W1, W2, Y, R1, Z, Y? and R are as defined herein.

Abstract: Disclosed are ?-D-ribofuranosyl-pyrazolo[3,4-d]pyrimidine compounds, compositions and methods for treating viral infections caused by a flaviviridae family virus, such as hepatitis C virus. Representative compounds include those having the general formula.

Abstract: The present invention relates to mononucleoside phosphate compounds that have the benefits of a dinucleotide pharmaceutical. These mononucleoside phosphates can be made from a mononucleotide that has been modified by attaching a degradation-resistant substituent on the terminal phosphate of a polyphosphate mononucleotide. By attaching this degradation-resistant substituent, the stability from degradation matches or exceeds those of certain dinucleotides. The mononucleoside phosphate compounds of the present invention are useful in preventing and treating epithelial tissue diseases or diseases or disorders associated with platelet aggregation.

Abstract: The invention relates to analogous compounds of 6-thioguanosine triphosphate of general formula (I). A compound of the general formula (I); wherein the dashed bond in the sugar moiety can be either single or double and wherein R1, R2, R3, R4 or R5, equal or different between each other, have general formula -(Int)m-Ter, wherein m is between 0 and 12 and Int and Ter are Internal and Terminal building blocks, wherein Int is selected from the group consisting of formula (II); and Ter is selected from the group consisting of formula (III).

Abstract: The present invention provides the use of ATP for the manufacture of a medicine comprising ATP as an active ingredient for exerting a preventive or therapeutic pharmacological effect when administered to a mammal, preferably a human, selected from the group consisting of: a. modulating oxidative stress and the effects thereof by favourably affecting the formation or scavenging of aggressive hydroxyl radicals; b. modulating the inflammatory response to a strong external insult such as endotoxin (LPS) and/or phytohaemagglutinin, even under conditions of severe oxidative stress; c. inhibiting the inflammatory response to a strong external insult such as endotoxin (LPS) and/or phytohaemagglutinin under conditions of severe oxidative stress; d. exerting a local protective effect against oxidative stress in the intestine, thus preventing intestinal damage induced by several types of medication such as non steroid anti-inflammatory drugs (NSAIDs); e.

Abstract: A method for preparing a nucleic acid probe is provided. The method comprises forming an activated cytosine or cytidine by a bisulfite catalyzed reaction; and covalently linking a reporter molecule to the activated cytosine or cytidine, wherein said activating step, said covalently linking step, or both are conducted in the presence of microwave energy. Also provided by the invention are nucleic acid probes.

Abstract: The invention describes novel nitrosated and/or nitrosylated compounds of the invention and pharmaceutically acceptable salts thereof, and novel compositions comprising at least one nitrosated and/or nitrosylated compound of the invention, and, optionally, at least one nitric oxide donor and/or at least one therapeutic agent. The invention also provides novel compositions comprising at least one compound of the invention, and at least one nitric oxide donor and/or at least one therapeutic agent. The invention also provides novel kits comprising at least one compound of the invention, that is optionally nitrosated and/or nitrosylated, and, optionally, at least one nitric oxide donor and/or at least one therapeutic agent. The invention also provides methods for (a) treating bacterial infections; (b) treating viral infections; (c) treating fungal infections; and (d) treating lesions.

Abstract: The present invention relates to mononucleoside phosphate compounds that have the benefits of a dinucleotide pharmaceutical. These mononucleoside phosphates can be made from a mononucleotide that has been modified by attaching a degradation-resistant substituent on the terminal phosphate of a polyphosphate mononucleotide. By attaching this degradation-resistant substituent, the stability from degradation matches or exceeds those of certain dinucleotides. The mononucleoside phosphate compounds of the present invention are useful in preventing and treating epithelial tissue diseases or diseases or disorders associated with platelet aggregation.

Abstract: The disclosed invention provides compositions and methods of treating a Flaviviridae infection, including hepatitis C virus, West Nile Virus, yellow fever virus, and a rhinovirus infection in a host, including animals, and especially humans, using a (2?R)-2?-deoxy-2?-fluoro-2?-C-methyl nucleosides, or a pharmaceutically acceptable salt or prodrug thereof.

Abstract: Labeled nucleotide analogs used in place of naturally occurring nucleoside triphosphates or other analogs in template directed nucleic acid synthesis reactions and other nucleic acid reactions, and various analyses based thereon, including DNA sequencing, single base identification, hybridization assays and others.

Abstract: The present invention provides the use of analogues and derivatives of dinucleoside polyphosphates with formula (I) or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for use in one or more of: the treatment of ischemia, inducing ischemic tolerance, modulating cerebral ischemia, to delay the onset of a hypoxic depolarisation stage when ischemic events are initiated; as a neurological protection agent; as a tissue protection agent; the treatment of pain; and the treatment of inflammation, wherein X, is selected from wherein X1 and X2 are independently selected from H, Cl, Br and F; each Y is independently selected from S and O; each Z is independently selected from —CX3X4—,—NH—,—O—; wherein X3 and X4 are selected from H, Cl, Br and F; B1 and B2 are independently selected from adenine, guanine, xanthine, thymine, uracil, cytosine and inosine; S1 and S2 are independently selected from ribose, open chain ribose, 2?-deoxyribose, 3?deoxyribose and arabinofuranoside.

Abstract: A method and composition for treating a host infected with flavivirus, pestivirus or hepacivirus comprising administering an effective flavivirus, pestivirus or hepacivirus treatment amount of a described base-modified nucleoside or a pharmaceutically acceptable salt or prodrug thereof, is provided.

Abstract: The invention provides molecules and methods for nucleic acid synthesis reactions useful in sequencing-by-synthesis processes.

Abstract: Disclosed are compounds, compositions and methods for treating viral infections caused by a flaviviridae family virus, such as hepatitis C virus. Such compounds are represented by Formula I as follows: wherein W, W1, W2, Y, R1, Z, Y? and R are as defined herein.

Abstract: Disclosed are compounds, compositions and methods for treating viral infections caused by a flaviviridae family virus, such as hepatitis C virus. Such compounds are represented by Formula IB as follows: and pharmaceutically acceptable prodrugs and salts thereof, where R, R1, R13, R14, W, W2, W3, Y and Z are as defined herein.

Abstract: Disclosed are compounds, compositions and methods for treating viral infections caused by a flaviviridae family virus, such as hepatitis C virus.