Abstract: A diagnostic method of monitoring anti-inflammatory and/or antioxidant actions of therapeutic agents comprises determining the level of at least one systemic marker indicative of inflammation or oxidation in a bodily sample taken from a subject at base line or following administration of the therapeutic agent. The marker includes at least one of MPO activity, MPO mass, select MPO-generated oxidation products, and combinations thereof. The level of the systemic marker is compared with a predetermined value to monitor the anti-inflammatory and/or antioxidant actions of the therapeutic agent.

Abstract: Methods for screening for neurological disorders are disclosed. Specifically, methods are disclosed for screening for neurological disorders in a subject by analyzing a tissue sample obtained from the subject for the presence of elevated levels of neurotoxic amino acids or neurotoxic derivatives thereof associated with neurological disorders. In particular, methods are disclosed for diagnosing a neurological disorder in a subject, or predicting the likelihood of developing a neurological disorder in a subject, by determining the levels of ?-N-methylamino-L-alanine (BMAA) in a tissue sample obtained from the subject. Methods for screening for environmental factors associated with neurological disorders are disclosed. Methods for inhibiting, treating or preventing neurological disorders are disclosed.

Abstract: The present invention provides, as a method of analyzing the C-terminal amino acid sequence of a peptide with use of reaction technique for successively releasing the C-terminal amino acids, in which undesirable side reactions, such as cleavage of a peptide bond at the middle of the peptide, can be prevented and chemical treatments therein can be carried out under widely applicable conditions in the course of successive release of the C-terminal amino acids from a peptide, such a method comprising steps of dehydrating the gel on which a target peptide that has been separated by gel electrophoresis is held in the bound state; immersing it in a mixture solution of an alkanoic acid anhydride added with a small amount of a perfluoroalkanoic acid in a dipolar aprotic solvent to re-swell the gel carrier, forming a 5-oxazolone structure, at a temperature chosen in the range of from 30° C. to 80° C.

Abstract: The invention provides methods to detect cysteine which employ oligonucleotide functionalized nanoparticles.

Abstract: The present invention provides, as for a method for analyzing the C-terminal amino acid sequence of a peptide by using a reaction for successively releasing the C-terminal amino acids of the peptide, which method can suppress, when successively releasing the C-terminal amino acids of a peptide of long amino acid length, such a undesirable side reaction as cleavage of peptide bond in the intermediate position of the peptide and can carry out the chemical treatment thereof under widely applicable conditions, a following method wherein a dry sample of a peptide with long amino acid length is beforehand subjected to an N-acylation treatment; by using a reaction reagent where an alkanoic acid anhydride is combined with a small amount of a perfluoroalkanoic acid, successive release of C-terminal amino acids is conducted under mild conditions; a hydrolysis treatment is applied; then, selective fragmentization at site of arginine residue is performed by digestion by trypsin; thereafter, decreases in molecular weight

Abstract: In an in vitro diagnostic test for osteoarthritis or rheumatoid arthritis, the amount or presence in a sample of anisomerised or optically inverted protein fragment is measured which derives from perlecan, bigylcan, decorin, fibrillin-1 or protocadherin or which is a specific sequence from aggrecan, type II collagen, COMP or CILP.

Abstract: The present disclosure provides the asymmetric cyanine fluorescent dyes of formula I in which X, n, R1, R2, R3, R4, R5 and Y? are as defined in the specification. The present disclosure also provides conjugates of the fluorescent dyes, methods for preparation thereof, compositions comprising the fluorescent dyes, and methods for staining biological samples using the fluorescent dyes and compositions thereof.

Abstract: The present invention relates to novel therapeutic uses of tianeptine, salts, isomers, pro-drugs, metabolites and structural analogs thereof. Furthermore, the present invention relates to the use of tianeptine, salts, isomers, pro-drugs, metabolites and structural analogs thereof, in obtaining methods of screening and of developing drugs. Finally, the present invention relates to the novel therapeutic use of other glutamine synthetase (GS) ligands and to the use of these ligands in obtaining methods for screening and developing drugs.

Abstract: A method for analyzing a plurality of amino acids in a fluid sample by a user is provided comprising the steps of introducing the sample into a buffer solution, passing the sample in the buffer solution through a separation column and setting a lithium ion concentration in the buffer to no more than 0.3 mols/L up to a time before ?-aminoisobutyric acid (?-AiBA) is eluted.

Abstract: The disclosed technology relates to the analysis of dissociation spectrum data that includes spectral peaks that represent fragments of a parent ion. The parent ion includes molecular subunits that are connected at cleavage sites. The technology accesses the dissociation spectrum data and determines a reference mass of one of the fragments where at least one of the molecular subunits in the fragment is unknown. The technology also selects a candidate parent ion description from a database of molecule descriptions where a computed ion mass of the candidate parent ion description matches the reference mass and scores the candidate parent ion description.

Abstract: The present invention provides a method for analyzing the C-terminal amino acid sequence of a peptide by applying reaction technique for successively releasing the C-terminal amino acids therefrom, which method can suppress, when releasing the C-terminal amino acids of the peptide in sequence, such as an undesirable side reaction as cleavage of peptide bond in the intermediate position of the peptide, and allows to carry out the chemical treatment thereof under widely applicable conditions. In the method according to the present invention, an alkanoic acid anhydride and a perfluoroalkanoic acid both of vapor phase, which are supplied from a mixture containing an alkanoic acid anhydride with a small amount of a perfluoroalkanoic acid added thereto, are allowed to act on a dry sample of the peptide to be examined in a dry atmosphere at a temperature chosen in a range of 15 to 60° C.

Abstract: Apparatus, methods, and program products are disclosed that classify spectral peaks in dissociation spectrum data and thereby improves the efficiency of molecular sequencing.

Abstract: The present invention provides solid-phase saccharide dyes. The dyes are bisboronic acids covalently bonded to a solid substrate. The dyes selectively conjugate with saccharides, particularly glucose, and register a signal. The signal is proportional to the quantity of saccharide. Thus, the dyes of the present invention are useful for measuring and monitoring saccharide levels, particularly in biological fluids such as blood.

Abstract: The present invention provides a method for acylating one or more amino groups of a peptide where the acylation reaction is to be performed in an aqueous mixture containing less than 10% w/w aprotic polar solvent.

Abstract: Methods for screening for neurological disorders are disclosed. Specifically, methods are disclosed for screening for neurological disorders in a subject by analyzing a tissue sample obtained from the subject for the presence of elevated levels of neurotoxic amino acids or neurotoxic derivatives thereof associated with neurological disorders. In particular, methods are disclosed for diagnosing a neurological disorder in a subject, or predicting the likelihood of developing a neurological disorder in a subject, by determining the levels of ?-N-methylamino-L-alanine (BMAA) in a tissue sample obtained from the subject. Methods for screening for environmental factors associated with neurological disorders are disclosed. Methods for inhibiting, treating or preventing neurological disorders are disclosed.

Abstract: A compound linked to a solid support (R) through a divalent linker moiety (X) and which is represented by the following formula: is disclosed. In particular, the 1-hydroxybenzotriazole-6-carboxylic acid is directly linked to the support under mild conditions (i.e., in aqueous or organic solvents at neutral pH and at room temperature). The polymer bound 1-hydroxybenzotriazole-6-carboxylic acid can be used for the derivatization of amines as well as for single step amino group modification of proteins, peptides, and amines via acylation or sulfonylation reactions. A flow through device and method for the single step amino group modifications of proteins, peptides, and amines is disclosed. Also disclosed is a flow through device for the detection of amines in a sample. Additionally, a device and method for the detection of amines in a sample using 1-hydroxybenzotriazole-6-carboxylic acid is disclosed. In a preferred embodiment, the device is used to detect the presence of amines in a spoiled meat product.

Abstract: A method is disclosed whereby the concentration of a blood substitute, such as cross-linked hemoglobin, in a serum or plasma specimen is rapidly and accurately identified and quantified. The method further takes the measured concentration of the blood substitute and uses it to correct for its effect, if any, on a measured analyte concentration, e.g., serum/plasma total protein. Further, the method allows for the determination of the concentration of true hemoglobin in the presence of blood substitutes. The method is carried out in respect of samples contained in a primary or secondary labelled tube, or a pipette tip used to dispense serum or plasma in a blood analyzer.

Abstract: The present invention exploits the discovery that amounts of uracil and thymine metabolites, especially ?-aminoisobutyric acid, in various bodily fluids, especially urine, are correlated with the occurrence of epilepsy when compared to matched control subjects. Analytical and diagnostic protocols, including a novel high performance liquid chromatography system, for use in the invention are disclosed.

Abstract: The instant invention involves the use of a combination of preparatory steps in conjunction with mass spectroscopy and time-of-flight detection procedures to maximize the diversity of biopolymers which are verifiable within a particular sample. The cohort of biopolymers verified within such a sample is then viewed with reference to their ability to evidence at least particular disease state; thereby enabling a diagnostician to gain the ability to characterize either the presence or absence of at least one disease state relative to recognition of the presence and/or the absence of the biopolymer.

Abstract: The instant invention involves the use of a combination of preparatory steps in conjunction with mass spectroscopy and time-of-flight detection procedures to maximize the diversity of biopolymers which are verifiable within a particular sample. The cohort of biopolymers verified within such a sample is then viewed with reference to their ability to evidence at least particular disease state; thereby enabling a diagnostician to gain the ability to characterize either the presence or absence of at least one disease state relative to recognition of the presence and/or the absence of the biopolymer.

Abstract: A system and method for desorption and ionization of analytes in an ablation medium. In one embodiment, the method includes the steps of preparing a sample having analytes in a medium including at least one component, freezing the sample at a sufficiently low temperature so that at least part of the sample has a phase transition, and irradiating the frozen sample with short-pulse radiation to cause medium ablation and desorption and ionization of the analytes. The method further includes the steps of selecting a resonant vibrational mode of at least one component of the medium and selecting an energy source tuned to emit radiation substantially at the wavelength of the selected resonant vibrational mode. The medium is an electrophoresis medium having polyacrylamide. In one embodiment, the energy source is a laser, where the laser can be a free electron laser tunable to generate short-pulse radiation. Alternatively, the laser can be a solid state laser tunable to generate short-pulse radiation.

Abstract: A novel method for the determination of amino acids by HPLC using pre-column derivatization is described. In this procedure, the aminno acids are derivatized with 2-chlorobenzoxazole to yield highly fluroresent N-(2-benzoxazolyl)-amino acids (BOX-AAs) for detection at very high sensitivity. Derivatives can also be detected using conventional UV detection methods. The BOX-AAs can be separated on a C18 reversed phase column for quantitative estimation. This method can be used for the preparation of N-(2-benzoxazolyl)-amino acids in large amounts.

Abstract: Disclosed is a method of reducing photooxidation or air oxidation in susceptible materials such as food, plastics or pharmaceuticals comprising mixing the material with an antioxidation composition comprising at least one amino acid, at least one metal ion, and at least one carboxylic acid in an amount effective to reduce photooxidation in the material.

Abstract: With rotating and translating a rotation-translation drum installed in a vacuum chamber of a mass spectrometry interface to constitute a mass spectro-meter, a liquid sample incorporating a dissolved substance to be analyzed in its mass is emitted for the drum from a sample supplying nozzle of the mass spectrometry interface, and the dissolved substance is isolated as a spiral filament on the drum. Then, a laser beam is irradiated onto the filament from a laser source via a laser beam inlet situated at the vacuum chamber and thereby, the dissolved substance is ionized without exposing to the air.

Abstract: A method is provided for joining a microchip device to a capillary tube. The microchip device has a capillary channel opening onto an edge surface of the device. A short hole is drilled into the edge surface, aligned with the capillary channel. The drilling is done with a flat bottom, preferably by a two-step drilling process. Then, the end of the capillary can be inserted into the hole so that its end is substantially flush with the flat bottom of the hole, thereby eliminating dead volume. Testing has shown that this connection provides very little band broadening of samples transported through the capillary channel into the capillary tube. The tip of the capillary tube can be tapered, so that it is suitable for use as an electrospray source for a mass spectrometer.

Abstract: The present invention relates to a method for generating a library of peptides based on a peptide of a predetermined molecular mass and to a method of determining the amino acid sequence of the peptide from the library. A set of amino acids that can be present in the peptide are defined, and an allowed library of all possible sequences of the amino acids in the set having a total mass equal to the predetermined molecular mass, allowing for water lost in forming peptide bonds and for protonation, is generated. The allowed library may be generated by first generating a set of all combinations of amino acids having a total mass equal to the predetermined molecular mass of the peptide and then calculating all linear permutations of all amino acids in each such combination. Generally, the molecular mass is determined using a mass spectrometer. A theoretical fragmentation spectrum for every amino acid sequence in the allowed set may also be calculated for use in determining the amino acid sequence of the peptide.

Abstract: The use of caspase inhibitors for treating, ameliorating, and preventing non-cancer cell death during chemotherapy and radiation therapy and for treating and ameliorating the side effects of chemotherapy and radiation therapy of cancer is disclosed.

Abstract: The present invention exploits the discovery that amounts of uracil and thymine metabolites, especially &bgr;-aminoisobutyric acid, in various bodily fluids, especially urine, are correlated with the occurrence of epilepsy when compared to matched control subjects. Analytical and diagnostic protocols, including a novel high performance liquid chromatography system, for use in the invention are disclosed.

Abstract: The present invention relates to methods and compositions for lipid matrix-assisted chemical ligation and synthesis of membrane polypeptides that are incorporated in a lipid matrix. The invention is exemplified in production of a prefolded membrane polypeptide embedded within a lipid matrix via stepwise chemoselective chemical ligation of unprotected peptide segments, where at least one peptide segment is embedded in a lipid matrix. Any chemoselective reaction chemistry amenable for ligation of unprotected peptide segments can be employed. Suitable lipid matrices include liposomes, micelles, cell membrane patches and optically isotropic cubic lipidic phase matrices. Prefolded synthetic and semi-synthetic membrane polypeptides synthesized according to the methods and compositions of the invention also permit site-specific incorporation of one or more detectable moieties, such as a chromophore, which can be conveniently introduced during synthesis.

Abstract: Provided is a method for acylating one or more amino groups of a peptide or protein such as GLP-1. This method includes (a) reacting a peptide or protein having at least one free amino group with an acylating agent of formula I wherein n is 0-8; R1 is COOR4; R2 is a lipophilic moiety; R3 and its attached carboxyl group designate a reactive ester or a reactive N-hydroxy imide ester; and R4 is selected from hydrogen, C1-12-alkyl and benzyl, under basic conditions in a mixture of an aprotic polar solvent and water; and (b) if R4 is not hydrogen, saponifying the acylated peptide or protein ester group under basic conditions in order to obtain an N-acylated peptide or an N-acylated protein.

Abstract: The present invention relates to a method of identifying a molecule of a molecule-substrate complex, wherein the molecule is covalently attached directly to a substrate or indirectly by means of a linking moiety, comprising: (a) bombarding the molecule-substrate complex with energized particles to cleave the molecule from the molecule-substrate complex; and (b) determining the molecular weight of the cleaved molecule by means of mass spectrometry. The inventive method may further comprise irradiating the cleaved molecule with photons.

Abstract: The present invention relates to a biodegradable amino-carboxylic acid chelating agent excellent in biodegradability and for use as a chelating agent, which is in the form of a solid, aqueous solution or slurry excellent in handling ability, wherein the chelating agent comprises a detergent composition having excellent detergency and high biodegradability.

Abstract: The present invention relates to a method of identifying a molecule of a molecule-substrate complex, wherein the molecule is covalently attached directly to a substrate or indirectly by means of a linking moiety, comprising: (a) bombarding the molecule-substrate complex with energized particles to cleave the molecule from the molecule-substrate complex; and (b) determining the molecular weight of the cleaved molecule by means of mass spectrometry. The inventive method may further comprise irradiating the cleaved molecule with photons.

Abstract: A sample presentation device, with a surface-bound complex including at least one molecule which chemically modifies a biomolecule, is prepared and exposed to a biomolecule. The molecular weights of the chemically modified biomolecule is then determined by mass spectrometry.

Abstract: The present invention provides a method for producing a peptide thiol ester using fluoren-9-ylmethoxycarbonylamino acid (Fmoc-amino acid). The method is for peptide synthesis and involves (1) using and removing the Fmoc group bound as the protective group to the amino group of amino acid, fixed on a resin via the thiol ester bond, a specific reagent is used to remove an Fmoc group from the amino acid thiol ester resin; (2) adding Fmoc-amino acid to the Fmoc-freed resin and then removing the Fmoc group, repeatedly, to prepare the Fmoc-peptide thiol ester resin; and (3) treating sequentially, the Fmoc-peptide thiol ester resin with a cleavage reagent and with a reagent capable of removing the Fmoc group.

Abstract: The invention includes compositions comprising and methods of using 1,2-indanedione derivatives for detecting an amine compound such as an amino acid. Methods of detecting and recording the pattern of a fingerprint on a surface are also included, as are a kit for detecting an amine compound such as a constituent of a fingerprint. The invention further includes a device for developing a fingerprint and a method of making 1,2-indanedione derivatives.

Abstract: A process is disclosed for sequencing proteins or peptides from the C-terminal end. The process comprises the steps of reacting the peptide or protein with an alkyl acid anhydride to convert the carboxy-terminal thereof into oxazolone, liberating the C-terminal amino acid by reaction with acid and alcohol or with ester, and identifying the liberated amino acid or amino acid derivative.

Abstract: A sample presentation device, with a surface-bound complex including at least one molecule which chemically modifies a biomolecule, is prepared and exposed to a biomolecule. The molecular weights of the chemically modified biomolecule is then determined by mass spectrometry.

Abstract: The present invention relates to cysteine protease inhibitors of the general formula (I): ##STR1## wherein Z is a cysteine protease binding moiety; X and Y are S, O or optionally substituted N; and R.sub.1 is optionally substituted alkyl or aryl.

Abstract: The present invention provides for an efficient and novel method for the C-terminal sequencing of proteins or peptides by use of acetyl chloride or phosphoryl chloride by reaction with a suitable isothiocyanate for derivitation of the carboxy terminus to a thiohydantoin amino acid derivative, under acidic conditions. Cleavage of the derivatized thiohydantoin amino acid may occur by use of thiocyanic acid and acetic acid in water and also by the novel means using a buffer and a potassium or sodium thiocyanate or potassium or sodium dithionite reagent. The present invention also provides for an novel and efficient means for the C-terminal sequencing of proteins or peptides by a two or three step process which comprises first reacting the peptide or protein with an acid chloride reagent, such as acetyl chloride, or phosphoryl chloride.

Abstract: A novel method for monitoring the success or the yield of chemical reactions involving a reactant bound to a solid phase support, or to forecast the success of such reactions, or to quantify the number of deuterium containing groups present in a solid-phase bound sample, using infrared spectroscopy and deuterium-carbon absorbances, along with novel compounds and intermediates useful for carring out the method.

Abstract: A synthetic strategy for the creation of large scale chemical diversity. Solid-phase chemistry, photolabile protecting groups, and photolithography are used to achieve light-directed spatially-addressable parallel chemical synthesis. Binary masking techniques are utilized in one embodiment. A reactor system, photoremovable protective groups, and improved data collection and handling techniques are also disclosed. A technique for screening linker molecules is also provided.

Abstract: A method of forming a thiohydantoin from an N-protected amino acid is described. The method employs a phosphate compound selected from the group consisting of(R.sub.1 O)(R.sub.2 O)P(.dbd.O)X and(R.sub.1 O)(R.sub.2 O)P(.dbd.O)--O--P(.dbd.O)(OR.sub.3)(OR.sub.4)to form acylphosphate moieties from the carboxyl groups of internal aspartic acid and glutamic acid residues and an acylphosphate moiety at a C-terminal carboxyl. The later acylphosphate, unlike the internal acylphosphates, spontaneously cyclizes to an oxazolone, which is less reactive with nucleophilic reagents. R.sub.1 and R.sub.2 are each alkyl, aryl, or alkaryl groups which are the same or different and which may be covalently linked to each other; R.sub.3 and R.sub.4 are each alkyl, aryl, or alkaryl groups which are the same or different and which may be covalently linked to each other; and X is a leaving group, such as chlorine or bromine, which is substantially unreactive towards thiohydantoins.

Abstract: The present invention provides for an efficient and novel method for the C-terminal sequencing of proteins or peptides by use of acetyl chloride or phosphoryl chloride by reaction with a suitable isothiocyanate for derivitazation of the carboxy terminus to a thiohydantoin amino acid derivative, under acidic conditions. Cleavage of the derivatized thiohydantoin amino acid may occur by use of thiocyanic acid and acetic acid in water and also by the novel means using a buffer and a potassium or sodium thiocyanate or potassium or sodium dithionite reagent. The present invention also provides for an novel and efficient means for the C-terminal sequencing of proteins or peptides by a two or three step process which comprises first reacting the peptide or protein with an acid chloride reagent, such as acetyl chloride, or phosphoryl chloride.

Abstract: The instant invention provides a library of bio-oligomers of defined size and known composition, in which the library contains all of the possible sequences of the bio-oligomers, and a method of synthesis thereof. The bio-oligomers of the library may be peptides, nucleic acids, or a combination of the foregoing. The instant invention also provides methods to identify bio-oligomers from a library that demonstrate desired characteristics such as binding, bioactivity and catalytic activity. Thus the instant invention provides a unique and powerful method to identify a useful bio-oligomer sequences from a library more quickly than current state-of-the-art technology allows. Effector molecules for use in treatment or diagnosis of disease are also provided.

Abstract: In many separation techniques, such as field flow fractionation, liquid chromatography and electro-phoresis, chemical species form bands that migrate at different velocities. If the data-digitization rate and excitation intensity are both set to be optimal for the fastest migrating band, to compensate for different band velocities, both the data-digitization rate and the excitation intensity are decreased as a function of time by a factor equal to the migration time of the fastest migrating band to the separation time.

Abstract: The present invention relates to a method for peptide C-terminal fragment sequence analysis, in which the fragment collection is carried out on an allylamine group-derivatized polymer membrane or on allylamine group-derivatized glass fiber filter paper; the collected C-terminal fragment is immobilized thereon using a water-soluble carbodiimide etc.; and the obtained immobilized product is subjected directly to amino acid sequence analysis. The present invention also relates to an apparatus for collecting a peptide fragment. According to the method of the present invention, peptides which are rich in hydrophobic groups in their C-terminus and are therefore difficult to trap with polyvalent ion carriers, currently used in the gas-phase sequencer, can be completely analyzed up to their C-terminus. Also, amino acid sequence analysis can be made even when the amount of C-terminal fragments is very small.

Abstract: A method is provided for C-terminal sequencing of a protein or peptide. An important feature of the method is the formation of an oxazolone moiety at the C-terminus of a protein or peptide by treatment with acetic anhydride under basic conditions followed by conversion of the oxazolone to a thiohydantoin moiety by treatment with thiocyanate under acidic conditions. Yields of thiohydantoin are further enhanced by delivering thiocyanate as the conjugate acid of a sterically hindered alkylammnonium cation.

Abstract: An improved method for the N-terminal sequential degradation of proteins and peptides is disclosed. The protein or peptide to be sequenced is reacted with a compound effective to impart a tertiary amine functionality to the thiazolinone derivative of a cleaved terminal amino acid of the peptide.

Abstract: A novel method for the sequential degradation from the N-terminus of small samples of proteins or peptides. The released amino acids may be detected by mass spectrometry.