Abstract: The present invention provides bifunctional polymers, methods of preparing the same, and intermediates thereto. These compounds are useful in a variety of applications including the PEGylation of biologically active molecules. The invention also provides methods of using said compounds and compositions thereof.

Abstract: The invention relates to a method for aiding the diagnosis of a disorder in a subject, said method comprising; providing a sample from said subject wherein the sample comprises blood; assaying at least two characteristics of said sample, said characteristics selected from: the structural composition of a polypeptide comprised by said sample; a metabolite comprised by said sample; and a catalytic activity comprised by said sample, wherein each of said at least two characteristics is determined from a multiplexed analysis of the same sample. The invention also relates to certain compositions.

Abstract: The present invention provides a urea derivative or a salt thereof, which is useful as a therapeutic agent for thrombosis.

Abstract: Compounds of formula (I) are useful in treating conditions or disorders prevented by or ameliorated by histamine-3 receptor ligands. Also disclosed are pharmaceutical compositions comprising the histamine-3 receptor ligands and methods for using such compounds and compositions.

Abstract: Compounds having the structure: are HIV reverse transcriptase inhibitors, wherein A, X, Y, Z, R1 and R2 are defined herein. The compounds and their pharmaceutically acceptable salts are useful in the inhibition of HIV reverse transcriptase, the prophylaxis and treatment of infection by HIV and in the prophylaxis, delay in the onset, and treatment of AIDS. The compounds and their salts can be employed as ingredients in pharmaceutical compositions, optionally in combination with other antivirals, immunomodulators, antibiotics or vaccines.

Abstract: The invention relates to methods for the quantitative and qualitative detection of an analyte in an assay as well as appropriate reagents therefor, especially a carrier molecule to which one or several analyte-specific binding partners are bound and which is provided with additional binding points for a specific binding partner X or Y that is associated with a component of a signal-forming system. Also disclosed is the use of such a conjugate particularly in homogeneous binding tests.

Abstract: A phosphoprotein detection reagent that selectively binds phosphoamino acids. Methods of generating and employing the reagent are also provided, as are methods of detecting modulation of protein phosphorylation are disclosed. Methods of detecting a change in state of a cell are also disclosed. Additionally, a kit for the detection of phosphoproteins is also disclosed.

Abstract: Cyclic alkynes (e.g., cyclooctynes such as dibenzocyclooctynes) can be photochemically generated from cyclopropenones as disclosed herein. The cyclic alkynes can be reacted (e.g., in situ) with materials having alkyne-reactive groups (e.g., azide groups in a “click” reaction). In preferred embodiments, the generation and reaction of the cyclic alkyne can proceed in the absence of a catalyst (e.g., Cu(I)). These reactions can be useful, for example, for the selective labeling of living cells that are metabolically modified with azido-containing surface monosaccharides, or for light-directed surface patterning.

Abstract: The present invention provides bifunctional polymers, methods of preparing the same, and intermediates thereto. These compounds are useful in a variety of applications including the PEGylation of biologically active molecules. The invention also provides methods of using said compounds and compositions thereof.

Abstract: Disclosed herein are peptide, particularly dipeptide compounds and the application thereof to the detection or inhibition of AI virus. The peptide compounds are more stable and easier to synthesize and store than are antibodies. In addition, having strong binding forces for the H5 protein of AI virus, the peptide compounds are useful as capturers or inhibitors of AI virus.

Abstract: The present invention relates to a labeling reagent of formula: in which: R1 represents at least one detectable label, L and A are each a linker arm, n is an integer equal to 1, and u is an integer between 0 and 2. The present invention also describes a method of synthesizing said markers and also applications for the labeling of biological molecules, more particularly nucleic acids, with a labeling reagent bearing diazo and nitro functions. The invention is particularly suitable for use in the diagnostics field.

Abstract: The present invention relates to a temperature-stable labeling reagent of formula (0): in which: R1 represents H or an alkyl, aryl or substituted aryl group, R2 represents a detectable marker or at least two detectable markers interlinked by at least one multimeric structure, L is a linker arm comprising a linear chain of at least two covalent bonds and n is an integer equal to 0 or 1, R3 and R4 represent, independently of one another: H, NO2, Cl, Br, F, I, R2-(L)n-Y—X—, OR, SR, NR2, R, NHCOR, CONHR, COOR, —CO—NH—(CH2)3—(O—CH2—CH2)3—CH2—NH—R2, —CO—NH—(CH2)3—(O—CH2—CH2)4—CH2—NH—R2 with R=alkyl or aryl, A is a linker arm comprising at least one covalent double bond enabling the conjugation of the diazo function with the aromatic ring and u is an integer between 0 and 2, preferably 0 or 1, —Y—X— represents —CONH—, —NHCO—, —CH2O—, —CH2S—, —Z— represents —NH—, —NHCO—, —CONH— or —O—, m is an integer between 1 and 10, preferably between 1 and 3, and p is an integer between 1 and 10, preferably between 1 and 3

Abstract: The present invention provides novel reactive fluorescent compounds that incorporate stable isotopic (deuterium, 13-carbon, 15-nitrogen, 18-oxygen) substitutions. The invention includes the use of these compounds, in combination with non-isotopically substituted analogs, for the purification, identification and relative quantification of proteins, peptides, saccharides, metabolites, and other biologically important compounds by combining liquid chromatography (LC) and mass spectrometry (MS). Fluorescent labeling of target compounds in this manner provides orders-of-magnitude sensitivity enhancement over traditional stable isotope labels, and also affords the possibility of simultaneous multiplexed analysis due to the multiwavelength nature of different fluorophores.

Abstract: The invention provides flavivirus replication inhibitors of WNV and other flaviviruses, such as, for example, JEV, SLEV, AV, KV, JV, CV, YV, TBEV, DENV-1, DENV-2, DENV-3, DENV-4, YFV and MVEV. The invention further provides pharmaceutical compositions including one or more such flavivirus replication inhibitors. The invention further provides methods of treatment, prevention, inhibition or amelioration of one or more diseases associated with flavivirus replication including administering one or more such inhibitors or pharmaceutical compositions.

Abstract: The present invention relates generally to novel protein modification reagents for fractionation and quantitative (differential) profiling of proteins in a complex mixture. The reagents react with amino acids or other protein components or structures and function as mass tags. The present invention provides methods of making the protein modification reagents and methods of using the protein modification reagents for quantitative analysis of proteins.

Abstract: A method of measuring the binding activity of a test compound to a splicing factor 3b (SF3b), which comprises the following steps of: (a) contacting a labeled pladienolide compound and a test compound with a cell or a cell fraction; and (b) measuring the distribution of the bound labeled compound. The method enables to screen for a novel active compound capable of acting on (binding to) a pladienolide target molecule or the like.

Abstract: The present invention relates in general to labeling reagents useful for labeling biomolecules. In particular, the invention provides activated labeling reagents, methods of preparing the same, methods of using the labeled reagents for synthesizing a labeled biomolecule, kits that include reagents for a labeling a biomolecule and kits containing for labeled biomolecules.

Abstract: Methods and compositions for detecting free radicals, the compositions being spin trapping compounds comprising a nitrone having a detecting moiety and optionally having a targeting moiety for targeting the nitrone to an organ, a cell, an organelle or a molecule of interest for directly detecting free radicals, especially free radicals in biological samples.

Abstract: The present invention relates to the synthesis and characterisation of biotinylated analogue of N-arachidonoylethanolamine (AEA) and its use as a tool to study AEA transport and trafficking through biochemical and morphological techniques. In particular biotinylated AEA (b-AEA, for which we propose the common name MM22) is suitable to design highly sensitive and simple methods for the non-radioactive detection and quantitation of AEA from complex samples, which would offer a useful alternative approach to the routinely used radiometric assays. The invention also relates to the use of b-AEA as a potential therapeutic and diagnostic agent.

Abstract: The invention provides a reagent comprising an affinity tag, a detectable moiety, a linker, an isotope tag and a reactive group. The invention also provides methods of using a reagent of the invention. The methods can be used to label a polypeptide in a sample by contacting a sample with a reagent of the invention under conditions allowing the reactive group to bind to one or more polypeptides in the sample. The invention additionally provides methods of isolating, identifying and quantifying a polypeptide in a sample. The invention further provides methods of diagnosing a disease using a reagent of the invention.

Abstract: The present invention provides modified cycloalkyne compounds; and method of use of such compounds in modifying biomolecules. The present invention features a cycloaddition reaction that can be carried out under physiological conditions. In general, the invention involves reacting a modified cycloalkyne with an azide moiety on a target biomolecule, generating a covalently modified biomolecule. The selectivity of the reaction and its compatibility with aqueous environments provide for its application in vivo (e.g., on the cell surface or intracellularly) and in vitro (e.g., synthesis of peptides and other polymers, production of modified (e.g., labeled) amino acids).

Abstract: The present invention provides novel reactive fluorescent compounds that incorporate stable isotopic (deuterium, 13-carbon, 15-nitrogen, 18-oxygen) substitutions. The invention includes the use of these compounds, in combination with non-isotopically substituted analogs, for the purification, identification and relative quantification of proteins, peptides, saccharides, metabolites, and other biologically important compounds by combining liquid chromatography (LC) and mass spectrometry (MS). Fluorescent labeling of target compounds in this manner provides orders-of-magnitude sensitivity enhancement over traditional stable isotope labels, and also affords the possibility of simultaneous multiplexed analysis due to the multiwavelength nature of different fluorophores.

Abstract: A biotin-amino acid conjugate, wherein the carboxylic group of biotin and the ?-amino group of an amino acid is linked by an amide bond, is biocompatible and has an excellent gelation capability in an aqueous medium. Accordingly, a hydrogel prepared therefrom is useful as a drug delivery system.

Abstract: An improved method for protein labeling comprising the steps of providing a synthetic small molecule tag, providing a target protein to be tagged, providing at least two enzymes for catalyzing a conjugation reaction between the tag and the target protein, incubating the tag, the protein and the enzyme, and allowing the tag to conjugate to the target protein. The tag may embody at least one structural feature of an ubiquitin C-terminus, and the structural feature may comprise a recognition sequence that is recognizable by an ubiquitin activating enzyme.

Abstract: The present invention relates to magnetic fine particles having a lower critical solution temperature to which at least one substance selected from biotin and avidin is immobilized, and a method of converting a substance, a method of separating or concentrating a microorganism, a method of modifying a denatured protein, a method of detecting a nucleic acid, a separating agent, and a method of separating a biological substance using the same.

Abstract: The present invention is directed compounds for reversibly modification of biologically active molecules. Described are polyconjugates systems that incorporate targeting, anti-opsonization, anti-aggregation, and transfection activities into small biocompatible in vivo delivery conjugates. The use of reversible modification provides for physiologically responsive activity modulation.

Abstract: The invention relates generally to biotin-containing compounds that are useful as imaging agents and drug-delivery agents. Another aspect of the invention relates to the aforementioned compounds chelated to a metal atom. In a preferred embodiment, the metal atom is a gadolinium. Another aspect of the invention relates to a compound comprising three biotin moieties and a pharmaceutical agent covalently bound to a heterocyclic core. In certain embodiments, the pharmaceutical agent is an antibiotic, antiviral, or radionuclide. Another aspect of the present invention relates to a method of treating disease involving administering the compounds of the invention to a mammal. Another aspect of the present invention relates to a method of acquiring a magnetic resonance image using the compounds of the invention.

Abstract: Formula (I) compounds are described: Formula (I) where the radicals are as defined in the description, processes for their preparation, and their uses for the preparation of conjugates with radionuclides for use in human and animal therapy and diagnostics, particularly for the diagnosis and therapy of pathological conditions such as tumours.

Abstract: The present invention features a chemoselective ligation reaction that can be carried out under physiological conditions. In general, the invention involves condensation of a specifically engineered phosphine, which can provide for formation of an amide bond between the two reactive partners resulting in a final product comprising a phosphine moiety, or which can be engineered to comprise a cleavable linker so that a substituent of the phosphine is transferred to the azide, releasing an oxidized phosphine byproduct and producing a native amide bond in the final product. The selectivity of the reaction and its compatibility with aqueous environments provides for its application in vivo (e.g., on the cell surface or intracellularly) and in vitro (e.g., synthesis of peptides and other polymers, production of modified (e.g., labeled) amino acids).

Abstract: The present invention relates, in general, to isoprenylcysteine carboxylmethyltransferase (Icmt) and, in particular, to inhibitors of Icmt and to methods of disease treatment using same.

Abstract: The invention provides non-affinity based isotope tagged peptides, chemistries for making these peptides, and methods for using these peptides. In one aspect, tags comprise a reactive site (RS) for reacting with a molecule on a protein to form a stable association with the peptide (e.g., a covalent bond) and an anchoring site (AS) group for reversibly or removably anchoring the tag to a solid phase such as a resin support. Anchoring may be direct or indirect (e.g., through a linker molecule). Preferably, the anchoring site comprises a biotin compound. Preferably, the tag comprises a mass-altering label, such as a stable isotope, such that association of the tag with the peptide can be monitored by mass spectrometry. The reagents can be used for rapid and quantitative analysis of proteins or protein function in mixtures of proteins.

Abstract: The present invention relates to a temperature-stable labeling reagent of formula (0): in which: R1 represents H or an alkyl, aryl or substituted aryl group, R2 represents a detectable marker or at least two detectable markers interlinked by at least one multimeric structure, L is a linker arm comprising a linear chain of at least two covalent bonds and n is an integer equal to 0 or 1, R3 and R4 represent, independently of one another: H, NO2, Cl, Br, F, I, R2 —(L)n—Y—X—, OR, SR, NR2, R, NHCOR, CONHR, COOR, —CO—NH—(CH2)3—(O—CH2—CH2)3-CH2—NH—R2, —CO—NH—(CH2)3—(O—CH2—CH2)4—CH2—NH—R2 with R=alkyl or aryl, A is a linker arm comprising at least one covalent double bond enabling the conjugation of the diazo function with the aromatic ring and u is an integer between 0 and 2, preferably 0 or 1, —Y—X— represents —CONH—, —NHCO—, —CH2O—, —CH2S—, -Z-represents —NH—, —NHCO—, —CONH— or —O—, m is an integer between 1 and 10, preferably between 1 and 3, and p is an integer between 1 and 10, preferably between 1 and 3

Abstract: The present invention provides polymeric compounds that can form micelles in solutions. These compounds have a hydrophobic, core that is coupled to a plurality of hydrophilic moieties.

Abstract: A mutant hydrolase optionally fused to a protein of interest is provided. The mutant hydrolase is capable of forming a bond with a substrate for the corresponding nonmutant (wild-type) hydrolase which is more stable than the bond formed between the wild-type hydrolase and the substrate. Substrates for hydrolases comprising one or more functional groups are also provided, as well as methods of using the mutant hydrolase and the substrates of the invention. Also provided is a fusion protein capable of forming a stable bond with a substrate and cells which express the fusion protein.

Abstract: This invention relates to agents and conjugates that can be used to detect and isolate target components from complex mixtures such as proteins and protein fragments from biological samples from in vivo and in vitro sources. Agents comprise a detectable group bound to a photoreactive group. Conjugates comprise agents coupled to substrates by covalent bounds which can be selectively cleaved with the administration of electromagnetic radiation. Targets substances labeled with detectable molecules can be easily identified and separated from a heterologous mixture of substances. Exposure of the conjugate to radiation releases the target in a functional form and completely unaltered. Using photocleavable molecular precursors as the conjugates, label can be incorporated into macromolecules, the nascent macromolecules isolated and the label completely removed.

Abstract: The present invention provides a fused ring compound of the following formula [I] ? wherein each symbol is as defined in the specification, a pharmaceutically acceptable salt thereof, and a therapeutic agent for hepatitis C, which contains this compound. The compound of the present invention shows an anti-hepatitis C virus (HCV) action based on the HCV polymerase inhibitory activity, and is useful as a therapeutic agent or prophylactic agent for hepatitis C.

Abstract: The present invention relates to phosphate-binding compounds that find use in binding, detecting and isolating phosphorylated target molecules including the subsequent identification of target molecules that interact with phosphorylated target molecules or molecules capable of being phosphorylated. A binding solution is provide that comprises a phosphate-binding compound, an acid and a metal ion wherein the metal ion simultaneously interacts with an exposed phosphate group on a target molecule and the metal chelating moiety of the phosphate-binding compound forming a bridge between the phosphate-binding compound and a phosphorylated target molecule resulting in a ternary complex. The binding solution of the present invention finds use in binding and detecting immobilized and solubilized phosphorylated target molecules, isolation of phosphorylated target molecules from a complex mixture and aiding in proteomic analysis wherein kinase and phosphatase substrates and enzymes can be identified.

Abstract: Methods, compounds, compositions and kits that relate to pretargeted delivery of diagnostic and therapeutic agents are disclosed. In particular, methods for radiometal labeling of biotin and for improved radiohalogenation of biotin, as well as related compounds, are described. Also, clearing agents, anti-ligand-targeting moiety conjugates, target cell retention enhancing moieties and additional methods are discussed.

Abstract: The present invention discloses methods of determining highly precise interactions between the HERG ion channel and various compounds. The methods of the present invention utilize the nonsense codon suppression methods combined with heterologous in vivo expression in Xenopus oocytes.

Abstract: A novel class of imidazo heterocyclic compounds, pharmaceutical compositions comprising them and use thereof in the treatment and/or prevention of diseases and disorders related to the histamine H3 receptor. More particularly, the compounds are useful for the treatment and/or prevention of diseases and disorders in which an interaction with the histamine H3 receptor is beneficial.

Abstract: The present invention is directed to compounds and pharmaceutical compositions comprising the compounds which are inhibitors of the enzyme gamma secretase and which are useful in the treatment or prevention of diseases in which the beta-amyloid peptide is involved, such as Alzheimer's disease.

Abstract: A method for the conditioning of an extracorporeal device is described, as well as method for extracorporeal extraction of toxic material from mammalian body fluids in connection with diagnosis or treatment of a mammalian condition or disease, in which methods reagents having the ability to extract toxic material from mammalian body fluids are involved, and an extracorporeal device comprising said reagent.

Abstract: This invention relates to peptide-containing &agr;-ketoamide inhibitors of cysteine and serine proteases, methods for making these compounds, and methods for using the same.

Abstract: An isomer, enantiomer, diastereoisomer, or tautomer of a compound, represented by formula I: 1

Abstract: The invention provides a highly sensitive measurement and detection technique for dioxins, which has advantages inherent to immunoassay; and markers to be used in the technique.

Abstract: Benzimidazole derivatives and salts and prodrugs thereof are disclosed, together with methods for the treatment of cancers or viral infections in warm blooded animals by administration of these compounds. Such compounds may be used in combination with a chemotherapeutic agent and/or a potentiator.

Abstract: A novel class of imidazo heterocyclic compounds, pharmaceutical compositions comprising them and use thereof in the treatment and/or prevention of diseases and disorders related to the histamine H3 receptor. More particularly, the compounds are useful for the treatment and/or prevention of diseases and disorders in which an interaction with the histamine H3 receptor is beneficial.

Abstract: The present invention relates to pharmaceutical compositions containing, as active ingredient, a compound of formula: 1

Abstract: This invention provides a series of substituted benzimidazoles which are useful in treating or preventing a condition associated with an excess of neuropeptide Y. This invention also provides methods employing these substituted benzimidazoles as well as pharmaceutical formulations with comprise as an active ingredient one or more of these compounds.

Abstract: Nucleic acid labeling compounds containing heterocyclic derivatives are disclosed. The heterocyclic derivative containing 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.