Abstract: The invention provides a dinucleoside polyphosphate analogue, or a pharmaceutically acceptable salt thereof, for use in the inhibition (or down-regulation) of a pain, via a transducing ATP-gated P2X3 receptor, often by means of high-affinity desensitisation (HAD) mechanism.

Abstract: This disclosure provides systems and methods for sequencing nucleic acids using nucleotide analogues and translocation of tags from incorporated nucleotide analogues through a nanopore. In aspects, this disclosure is related to composition, method, and system for sequencing a nucleic acid using tag molecules and detection of translocation through a nanopore of tags released from incorporation of the molecule.

Abstract: Particular nucleoside 5?-phosphorothioate analogues, such as, adenosine or uridine 5?-di- or tri-phosphorothioate analogues in which at least one of the bridging oxygen atoms of the phosphorothioate is replaced by a group such as —CH2— or —CCl2—, and at least one of the non-bridging atoms or negatively-charged atoms of the phosphorothioate is either a sulfur atom or a sulfur ion can be formulated into pharmaceutical compositions. These compounds are useful for treatment of osteoarthritis/calcium pyrophosphate dihydrate (CPPD) deposition disease.

Abstract: Provided are a method of preparing a zinc oxide nanostructure electrode and a method of preparing a dye-sensitized solar cell using the same. The present invention relates to a use of nicotinic acid adenine dinucleotide phosphate or a derivative thereof for promoting the differentiation of keratinocytes into fibroblasts. The present invention provides a pharmaceutical or cosmetic use of a composition containing NAADP or a derivative thereof for regenerating and improving a skin barrier, or preventing, improving or treating stratum corneum disorders such as psoriasis or atopy, and a use for promoting the differentiation of separated keratinocytes.

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: Embodiments of the invention provide non-natural bifunctional nucleotides having both nuclease resistance and nucleic acid synthesis blocking properties and methods of sequencing nucleic acids that employ non-natural bifunctional nucleic acids. Additional embodiments provide non-natural oligonucleotides and methods for sequencing nucleic acids using the non-natural oligonucleotides. Methods according to embodiments of the invention employ electronic detection and fluorescent detection of nucleic acid sequencing reactions.

Abstract: The present invention provides labeled phospholink, nucleotides that can be used in place of naturally occurring nucleotide 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 invention features compounds of formula I and methods of their use as antiplatelet and antithrombotic compounds: H/N=Q?2OOOO?Q2-N, HR6/NIf)(^XMO-M??OM°?X1MQ?)r(^rfHOOHHOOQHiN?iR2 Formula (I).

Abstract: Provided are adenosine analog compounds of the general formula that act as P2Y receptors, e.g., the P2Y2 receptor, including pharmaceutical compositions; and uses thereof to treat or prevent diseases associated with that receptor, e.g., disorders relating to mucus secretion, such as cystic fibrosis, chronic obstructive pulmonary disorder (COPD), asthma, constipation, chronic idiopathic constipation, dry mouth (xerostomia), gum disease, and gastrointestinal problems caused by radiation and chemotherapy for cancer.

Abstract: This disclosure is related to a method of sequencing a single-stranded DNA using deoxynucleotide polyphosphate analogues and translocation of tags from incorporated deoxynucleotide polyphosphate analogues through a nanopore.

Abstract: The invention provides compounds and methods for making adenosine-ribofuranoside tetraphosphate compounds. The compounds are contemplated to have activity at the P2Y receptor and may be used in the treatment of medical disorders such as cystic fibrosis and upper respiratory disorders.

Abstract: Provided are a method of preparing a zinc oxide nanostructure electrode and a method of preparing a dye-sensitized solar cell using the same. The present invention relates to a use of nicotinic acid adenine dinucleotide phosphate or a derivative thereof for promoting the differentiation of keratinocytes into fibroblasts. The present invention provides a pharmaceutical or cosmetic use of a composition containing NAADP or a derivative thereof for regenerating and improving a skin barrier, or preventing, improving or treating stratum corneum disorders such as psoriasis or atopy, and a use for promoting the differentiation of separated keratinocytes.

Abstract: Alkynyl-derivatized cap analogs, alkynyl-modified capped RNA, 1,4-disubstituted triazole-derivatized capped RNA, methods of preparation, methods of isolation, and uses thereof are provided. The “click” modification facilitates detection and isolation of capped RNAs and the 1,4-disubstituted triazole derivatives formed by the “click” reaction are useful for producing RNA transcripts and encoded protein.

Abstract: The present disclosure provides modified nucleosides, nucleotides, and nucleic acids, and methods of using thereof.

Abstract: In general, the invention features methods and systems for sequencing of nucleic acids based on the measurement of the incorporation of fluorogenic nucleotides in microreactors. The invention provides numerous advantages over previous systems such as unambiguous determination of sequence, fast cycle time, long read lengths, low overall cost of reagents, low instrument cost, and high throughput. The invention also features methods and kits for nucleic acid amplification. The amplification and sequencing aspects of the invention may or may not be employed in conjunction with one another. The invention also features fluorogenic nucleotides that may be used in the sequencing methods of the invention.

Abstract: Novel cap analogs which are easily synthesized, resulting in high levels of capping efficiency and transcription and improved translation efficiencies are provided. Such caps are methylated at the N7 position of one or both guanosines of the dinucleotide cap as well as at the 3? position on the ribose ring. Substituent groups on the ribose ring also result in the cap being incorporated in the forward orientation. Also provided are methods useful for preparing capped analogs and using mRNA species containing such analogs are also contemplated herein, as well as kits containing the novel cap analogs.

Abstract: The synthesis of capped/tagged RNA, methods of use and kits providing same are contemplated. Tagged RNA permits isolation of RNA transcripts in vitro. The ability to isolate and purify capped RNA results in improved transcription and translation and provides a tool for identifying RNA-protein interactions. Such capped RNA finds use in therapeutic applications, diagnosis and prognosis and in the treatment of cancers and HIV.

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 present invention is directed to a method for treating cystic fibrosis. The method comprises the steps of: identifying a patient suffering from cystic fibrosis, and administering to the patient an effective amount of denufosol or a pharmaceutically acceptable salt thereof and an effective amount of a macrolide. In one method, denufosol and the macrolide are administered by inhalation, preferably in a single formulation. In another method, denufosol is administered by inhalation and the macrolide is administered orally. The present invention is also directed to a pharmaceutical formulation comprising denufosol or a pharmaceutically acceptable salt thereof, a macrolide, and a pharmaceutically acceptable carrier. Preferred denufosol is denufosol tetrasodium and preferred macrolide is azithromycin. The pharmaceutical formulation preferably is in a form of an inhalable dry powder or in a liquid form.

Abstract: The invention provides a novel class of scaffold-based labeled polymerase enzyme substrates. The polymerase enzyme substrates have a multivalent core or scaffold to which is attached fluorescent dye moieties and nucleoside phosphate moities. The polymerase enzyme substrates have multiple fluorescent dye moities and/or multiple nucleoside phosphate moieties. Preferred multivalent cores comprise trifunctional six membered aromatic moities. The invention also provides for sequencing methods and kits with scaffold-based labeled polymerase enzyme substrates.

Abstract: The present invention relates to a modified nucleotide and real-time polymerase reaction using the nucleotide. Specifically, the present invention relates to a fluorescence material linked-nucleotide, a composition for real-time polymerase reaction comprising the nucleotide, an analysis kit and an analysis method. In the present invention, the fluorescence material linked-nucleotide serves the dual roles of producing fluorescence signal as well as being used as a substrate. Therefore, the present invention is economically advantageous because it is unnecessary to prepare probes, but can be applied to analyze various real-time polymerase reactions such as PCR, RCA and isothermal polymerization reaction, and shows higher quality of performance than the past methods.

Abstract: In various embodiments, the present invention provides fluorescent dyes that are linked to another species through an adaptor moiety. In an exemplary embodiment, the dye is linked to a polyphosphate nucleic acid through an adaptor. An adaptor can be a component of a linker. These conjugates find use in single molecule DNA sequencing and other applications. In various embodiments, the dye moiety is a cyanine dye. Cyanine dyes that are highly charged, such as those including multiple sulfonate, alkylsulfonate, carboxylate and/or alkylcarboxylate moieties are examples of cyanine dyes of use in the compounds of the invention.

Abstract: In various embodiments, the present invention provides fluorescent dyes that are linked to another species through an amino acid or peptide linker. In an exemplary embodiment, the dye is linked to a polyphosphate nucleic acid through an amino acid or peptide linker. These conjugates find use in single molecule DNA sequencing and other applications. In various embodiments, the dye moiety is a cyanine dye. Cyanine dyes that are highly charged, such as those including muliple sulfonate, alkylsulfonate, carboxylate and/or alkylcarboxylate moieties are examples of cyanine dyes of use in the compounds of the invention.

Abstract: The invention provides prodrugs activated by RNA-dependent DNA-polymerases, and methods for treating hematological tumors, blood, and blood derivatives from patients affected by retroviral infections by administering the prodrugs. The invention also provides methods for the preparation of pharmaceutical compositions containing the prodrugs.

Abstract: Engineered nucleotide compositions, having polymerase interacting components that improve the interactivity of the polymerase and the nucleotide, particularly for nucleic acid sequencing applications. Compositions include the interactive polymerases along with the nucleotide analogs. Kits, methods and systems are provided for analysis of nucleoc acid synthesis reactions.

Abstract: Provided herein are heptamethine cyanine dyes having a large Stokes shift, and the salts and conjugates thereof. Also provided are methods of using and making such large Stokes shift dyes as fluorescence resonance energy transfer (FRET) acceptors or donors.

Abstract: The present invention encompasses compositions and methods that activate P2Y receptors for the increased production of new synapses in the central nervous system. The formulations of the invention may be administered to a healthy subject or to a subject in need thereof to restore synapses.

Abstract: The present invention provides a method of treating edematous retinal disorders. The method comprises administration of a pharmaceutical formulation comprising a hydrolysis-resistant P2Y receptor agonist to stimulate the removal of pathological extraneous fluid from the subretinal and retinal spaces and thereby reduce the accumulation of said fluid associated with retinal detachment and retinal edema. The P2Y receptor agonist can be administered with therapeutic and adjuvant agents commonly used to treat edematous retinal disorders. The present invention also provides a method of treating cystic fibrosis. The present invention also provides a method of treating sinusitis. The present invention further provides P1-(2?-deoxycytidine 5?-)P4-(uridine 5?-)tetraphosphate, tetra-(alkali metal) salts such as tetrasodium, tetralithium, tetrapotassium, and mixed (tetra-alkali metal) salts.

Abstract: Dinucleotide cap analogs are disclosed, modified at different phosphate positions with a boranophosphate group or a phosphoroselenoate group. The analogs are useful as reagents in the preparation of capped mRNAs and have increased stability both in vitro and in vivo. They may be used as inhibitors of cap-dependent translation. Optionally, the boranophosphate or phosphoroselenoate group has a 2?-O or 3?-O-alkyl group, preferably a methyl group, producing analogs called BH3-ARCAs or Se-ARCAs. ARCAs may be modified with ?-, ?-, or ?-boranophosphate or phosphoroselenoate groups.

Abstract: The present invention relates to a novel class of guanine nucleotide analogs which inhibit RelA and Relseq synthetic activity and which possess anti-bacterial activity. The present invention also relates to pharmaceutical compositions that include such compounds, and to methods of use of such compounds or compositions for combating bacteria and treating bacterial infections.

Abstract: This invention is directed to a method of enhancing or facilitating the clearance or the lung mucus secretions in a subject. This invention is also directed to a method of facilitating the hydration of the lung mucus secretions in a subject. This invention is further directed to a method of preventing or treating diseases or conditions associated with impaired lung or airway function in a human or other mammal. The method comprises administering to a subject a pharmaceutical composition comprising a therapeutic effective amount of P2Y6 receptor agonist compound, wherein said amount is effective to activate the P2Y6 receptors on the luminal surface of lung epithelia. The P2Y6 receptor agonist compounds useful for this invention include mononucleoside 5?-diphosphates, dinucleoside monophosphate, dinucleoside diphosphates, or dinucleoside triphosphates of general Formula I, or salts, solvates, hydrates thereof. This invention is also directed to novel P2Y6 receptor agonist compounds.

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 features compositions, methods, and systems for single-molecule sequencing of nucleic acids based on the continuous measurement of the incorporation of fluorogenic nucleotides in microreactors. In particular, the invention features fluorogenic compounds for use in nucleic acid sequencing. The invention provides numerous advantages over previous systems such as unambiguous determination of sequence, continuous sequencing, long read lengths, low overall cost, and ease of sample preparation.

Abstract: The invention provides for nucleotide analogs and methods of using the same, e.g., for sequencing nucleic acids.

Abstract: The present invention provides a method of treating edematous retinal disorders. The method comprises administration of a pharmaceutical formulation comprising a hydrolysis-resistant P2Y receptor agonist to stimulate the removal of pathological extraneous fluid from the subretinal and retinal spaces and thereby reduce the accumulation of said fluid associated with retinal detachment and retinal edema. The P2Y receptor agonist can be administered with therapeutic and adjuvant agents commonly used to treat edematous retinal disorders. The present invention also provides a method of treating cystic fibrosis. The present invention further provides P1-(2?-deoxycytidine 5?-)P4-(uridine 5?-) tetraphosphate, tetra-(alkali metal) salts such as tetrasodium, tetralithium, tetrapotassium, and mixed (tetra-alkali metal) salts. The present further provides a pharmaceutical formulation comprising a P1-(2?-deoxycytidine 5?-)P4-(uridine 5?-) tetraphosphate, tetra-(alkali metal) salt, in a pharmaceutically acceptable carrier.

Abstract: Novel compositions and methods are provided for identifying agents which affect chromosomal stability and aging.

Abstract: Alkyl-linked nucleotide non-homogeneous solid supports and nucleotide affinity media comprising an alkyl-linked nucleotide are provided. The linker is generally a hydrophobic linker that can be a 3, 4, 5, 6, 7, 8, 9, 10, or a longer carbon chain. Also included in the invention are methods for synthesis of an alkyl-linked nucleotide, nucleotide affinity media and methods of use thereof for affinity chromatography and screening methods.

Abstract: The present invention provides dinucleoside boranophosphate derivatives of the general formula I: wherein X and X? each independently is an unsubstituted or substituted purine or pyrimidine residue; Y and Y? each independently is H or OH; Z1 to Z5 each independently is O? or BH3?, but excluding the compounds wherein Z1 to Z5 are each O?; W1 to W4 each independently is O, CH2, NH or C(Halogen)2; n and n? each independently is 0 or 1; m is 3, 4 or 5; and M+ represents a pharmaceutically acceptable cation, and to pharmaceutical compositions thereof. These dinucleoside boranophosphates are useful for prevention or treatment of diseases or disorders modulated by P2Y receptors such as type 2 diabetes, cystic fibrosis and cancer.

Abstract: Novel compositions and methods are provided for identifying agents which affect chromosomal stability and aging.

Abstract: The present invention relates to nucleoside diphosphate mimics and nucleoside triphosphate mimics, which contain diphosphate or triphosphate moiety mimics and optionally sugar-modifications and/or base-modifications. The nucleotide mimics of the present invention, in a form of a pharmaceutically acceptable salt, a pharmaceutically acceptable prodrug, or a pharmaceutical formulation, are useful as antiviral, antimicrobial, and anticancer agents. The present invention provides a method for the treatment of viral infections, microbial infections, and proliferative disorders. The present invention also relates to pharmaceutical compositions comprising the compounds of the present invention optionally in combination with other pharmaceutically active agents.

Abstract: The present invention provides new methods for the synthesis of the therapeutic dinucleotide, P1,P4-di(uridine 5?)-tetraphosphate, and demonstrates applicability to the production of large quantities. The methods of the present invention substantially reduce the time period required to synthesize diuridine tetraphosphate, preferably to three days or less. The novel tetrammonium and tetrasodium salts of P1,P4-di(uridine 5?)-tetraphosphate (Formula I) prepared by these methods are stable, soluble, nontoxic, and easy to handle during manufacture. wherein: X is Na, NH4 or H, provided that all X groups are not H.

Abstract: The invention includes compositions and methods useful for treatment of a virus infection in a mammal by double-targeting the virus (i.e. targeting the virus at more than one stage of the virus life cycle) and thereby inhibiting virus replication. The compositions of the invention include compounds, which comprise a phosphocholine moiety covalently conjugated with one or more therapeutic agents (e.g. nucleoside analogue, protease inhibitor, etc.) to a lipid backbone. The invention also includes pharmaceutical compositions for use in treatment of a virus infection in mammals. The methods of the invention comprise administering a compound of the invention, a pharmaceutically acceptable salt or a prodrug thereof, or a pharmaceutical composition of the invention, in an amount effective to treat the infection, to a mammal infected with a virus.

Abstract: The present invention is directed to the field of organic chemistry in general and specifically to the preparation of hydrophobic derivatives of cyclic ADP ribose. One form of the present invention is the composition of one or more hydrophobic derivatives of cyclic ADP ribose. In another form of the present invention, a method for preparing a hydrophobic composition is described. Compositions of the present invention are useful for the study of in vivo calcium metabolism.

Abstract: Oligonucleotide probes containing two labels are provided and are useful in hybridization assays. The probes can also contain a minor groove binding group.

Abstract: The present invention are directed to P1, P4-di(uridine 5′)-tetraphosphate, tetra-alkali metal salts such as tetrasodium, tetralithium, tetrapotassium, and mixed tetra-alkali metal cations thereof. The tetra alkali metal salts of P1, P4-di(uridine 5′)-tetraphosphate are water-soluble, nontoxic, and easy to handle during manufacture. These tetra-monovalent alkali metal salts are more resistant to hydrolysis than the mono-, di-, or tri-acid salts, therefore, they provide an improved stability and a longer shelf life for storage. The present invention also provides methods for the synthesis of P1, P4-di(uridine 5′)-tetraphosphate, and its pharmaceutically acceptably acceptable salts thereof, and demonstrates the applicability to the production of large quantities. The methods substantially reduce the time required to synthesize diuridine tetraphosphate, for example, to three days or less.

Abstract: The invention includes compositions and methods useful for treatment of a virus infection in a mammal by double-targeting the virus (i.e. targeting the virus at more than one stage of the virus life cycle) and thereby inhibiting virus replication. The compositions of the invention include compounds which comprise a phosphocholine moiety covalently conjugated with one or more antiviral agents (e.g. nucleoside analogue, protease inhibitor, etc.) to a lipid backbone. The invention also includes pharmaceutical compositions and kits for use in treatment of a virus infection in mammals. The methods of the invention comprise administering a compound of the invention, a pharmaceutically acceptable salt thereof, or a pharmaceutical composition of the invention, in an amount effective to treat the infection, to a mammal infected with a virus. Additionally, the invention includes compositions and methods useful for combating a cancer in a mammal and for facilitating delivery of a therapeutic agent to a mammalian cell.

Abstract: The invention provides compounds comprising at least one phosphohalohydrin group of the formula: where X is a halogen selected from among I, Br, Cl, R1 is selected from among —CH3 and —CH2—CH3, Cat+ is an organic or inorganic cation, and n is an integer between 2 and 20, processes for the production thereof and uses thereof, in particular therapeutic uses and for activating primate T&ggr;9&dgr;2 lymphocytes.

Abstract: The present invention is directed to crystals of P1-(2′-deoxycytidine 5′-)P4-(uridine 5′-)tetraphosphate (dCP4U) or a salt thereof and to a process for producing the crystals. The present invention also provides a process for producing dCP4U involving reacting uridine 5′-monophosphate (UMP), 2′-deoxycytidine 5′-monophosphate (dCMP), diphenyl phosphorochloridate (DPC), and pyrophosphate (PPi). The crystals of dCP4U obtained through the process according to the present invention have high purity and high stability and no hygroscopicity as compared with a freeze-dried product, and thereby serve as a useful raw material for preparing a pharmaceutical. The process for producing dCP4U according to the present invention permits use of inexpensive UMP as a raw material and realizes high yield. Thus, the process is suitable for large-scale synthesis of dCP4U.

Abstract: The present invention provides methods for the synthesis of a pharmaceutically useful dinucleotide, P1, P4-di(uridine 5′)-tetraphosphate, and demonstrates the applicability to the production of large quantities. The methods of the present invention substantially reduce the time required to synthesize diuridine tetraphosphate, for example, to three days or less. The tetrasodium, ammonium, lithium and potassium salts of P1, P4-di(uridine 5′)-tetraphosphate prepared by these methods are stable, soluble, nontoxic, of high purity and easy to handle during manufacture.

Abstract: The present invention provides methods of preparing large polynucleotides of arbitrary sequence and in a manner that will readily lend itself to automation. The present invention provides methods of preparing a polynucleotide having at least 200 nucleotides in either a 5′ to 3′ or 3′ to 5′ direction by ligating a plurality of oligonucleotides, the assembly of which, represents the nucleotide sequence of the desired polynucleotide.