Abstract: The present invention relates to an isolated polypeptide having beta-lactamase activity and nucleic acid sequences encoding the polypeptide. The isolated polypeptide of the invention is a Verona integron-encoded metallo-?-lactamase (VIM-2) variant with improved properties such as improved protease stability, stability in intestinal medium, improved activity against one or more antibiotics, improved specific activity and/or improved production in a host cell.

Abstract: A reference solution is provided, which comprises, in a liquid phase, at least one of a first compound and a second compound which are mutually convertible into each other, and at least one catalyst, which catalyzes the conversion between the first compound and the second compound.

Abstract: Low-copper click chemistry, 1.3-dipolar cycloadditions, and Staudinger ligations for modifying biomolecules is provided. Compositions, methods, and kits relating to low-copper click chemistry, 1.3-dipolar cycloadditions, and Staudinger ligations are also provided.

Abstract: The present invention relates to a hydantoinase having an amino acid sequence selected from (i) or (ii), with (i) amino acid sequence selected from SEQ ID NO: 6-20 and SEQ ID NO: 73-119 (ii) amino acid sequence wherein in the amino acid sequence of SEQ ID NO: 6-20 and SEQ ID NO: 73-119, 1 to 75 amino acid residues have been substituted, deleted, inserted and/or added, and wherein further the catalytic activity of the hydantoinase is higher by a factor of at least 1.2 than the catalytic activity of the hydantoinase having amino acid sequence SEQ ID NO: 1, The present invention further relates to a process for preparing amino acids, wherein said hydantoinase is used.

Abstract: The present invention relates to pharmaceuticals and modified beta-lactamases. Specifically, the invention relates to novel recombinant beta-lactamases and pharmaceutical compositions comprising the beta-lactamases. Also, the present invention relates to methods for modifying a beta-lactamase, producing the beta-lactamase and treating or preventing beta-lactam antibiotic induced adverse effects. Furthermore, the present invention relates to the beta-lactamase for use as a medicament and to the use of the beta-lactamase in the manufacture of a medicament for treating or preventing beta-lactam antibiotics induced adverse effects. Still further, the invention relates to a polynucleotide and a host cell comprising the polynucleotide.

Abstract: The present invention relates to methods for determining the concentration of a free beta-lactam antibiotic in a biological sample. In particular, the present invention relates to methods for measuring a free beta-lactam antibiotic in a biological sample, comprising the steps of: (a) providing at least one class C beta-lactamase, a functional fragment or variant thereof; (b) providing at least one biological sample; (c) contacting said at least one class C beta-lactamase with said at least one biological sample; and (d) determining the concentration of said free beta-lactam antibiotic in said at least one biological sample.

Abstract: The present invention refers to a fusion protein biosensor, comprising a peptide or protein domain that binds an analyte of interest (A), an entity that can produce a detectable signal (B), and an entity that binds to B and modulate the signal produced by B when A is not bound to the analyte. A method and a kit for detecting a presence or amount of an analyte molecule using the fusion protein is also disclosed.

Abstract: The present invention relates to pharmaceuticals and modified beta-lactamases. Specifically, the invention relates to novel recombinant beta-lactamases and pharmaceutical compositions comprising the beta-lactamases. Also, the present invention relates to methods for modifying a beta-lactamase, producing the beta-lactamase and treating or preventing beta-lactam antibiotic induced adverse effects. Furthermore, the present invention relates to the beta-lactamase for use as a medicament and to the use of the beta-lactamase in the manufacture of a medicament for treating or preventing beta-lactam antibiotics induced adverse effects. Still further, the invention relates to a polynucleotide and a host cell comprising the polynucleotide.

Abstract: The present invention relates to pharmaceuticals and modified beta-lactamases. Specifically, the invention relates to novel recombinant beta-lactamases and pharmaceutical compositions comprising the beta-lactamases. Also, the present invention relates to methods for modifying a beta-lactamase, producing the beta-lactamase and treating or preventing beta-lactam antibiotic induced adverse effects. Furthermore, the present invention relates to the beta-lactamase for use as a medicament and to the use of the beta-lactamase in the manufacture of a medicament for treating or preventing beta-lactam antibiotics induced adverse effects. Still further, the invention relates to a polynucleotide and a host cell comprising the polynucleotide.

Abstract: The present invention provides diagnostic methods for determining the risk of developing an autism spectrum disorder (ASD) in a fetus or child by detecting in a biological sample from the mother antibodies that bind to one or more biomarkers selected from the group consisting of lactate dehydrogenase (LDH), guanine deaminase (GDA), collapsin response mediator protein 1 (CRMP1), stress-induced phosphoprotein 1 (STIP1), alpha subunit of the barbed-end actin binding protein Cap Z (CAPZA2), Y Box Binding Protein 1 (YBX1), eukaryotic translation and elongation factor 1A1 (EEF1A1), microtubule-associated protein Tau (MAPT), dihydropyrimidinase-like protein 2 (DPYSL2), dynamin 1-like protein (DNM1L), radixin (RDX), moesin (MSN), and ezrin (EZR).

Abstract: The present invention relates to stable cyanuric acid hydrolase enzymes, compositions, and devices for use in the treatment of a liquid, such as water. The present invention also relates to methods of using these enzymes, compositions and devices for the treatment of a liquid, such as water.

Abstract: The present invention has its object to provide a novel polypeptide having amidase activity to selectively hydrolyze S-enantiomer in racemic nipecotamide, a DNA encoding the polypeptide, a vector containing the DNA, a transformant transformed with the vector, and a method for producing an optically active carboxylic acid amide and an optically active carboxylic acid in which a racemic carboxylic acid amide is hydrolyzed with the polypeptide or the transformant.

Abstract: The present invention relates to compounds that are substrates for an enzyme, and upon reaction with the enzyme provide a detectable response, such as an optically detectable response. In particular, the compounds have utility in detecting the presence of a ?-lactamase in a sample. In addition to the compounds, methods are disclosed for analyzing a sample for the presence of a ?-lactmase, for example, as an indicator of expression of a nucleic acid sequence including a sequence coding for a ?-lactmase. Kits are disclosed that include the disclosed compounds and additional components, for example, cells, antibodies, a ?-lactmase or instructions for using the components in an assay.

Abstract: The present invention relates to a process for the biocatalytic, enantioselective production of a ?-amino acid pre-cursor from an optionally substituted dihydrouracil using a hydantoinase and/or a dihydropyrimidinase, a process for producing a ?-amino acid from said precursor, a hydantoinase and its use in said process for the biocatalytic production of a ?-amino acid pre-cursor or a ?-amino acid, and a method for obtaining said hydantoinase.

Abstract: The present invention relates to a carbapenemase and methods using said carbapenemase such as screening methods, predictive methods and therapeutic uses.

Abstract: Purified genes encoding a T cell surface antigen from a mammal, reagents related thereto including purified proteins, specific antibodies, and nucleic acids encoding this antigen are provided. Methods of using said reagents and diagnostic kits are also provided.

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: The present invention relates to stable cyanuric acid hydrolase enzymes, compositions, and devices for use in the treatment of a liquid, such as water. The present invention also relates to methods of using these enzymes, compositions and devices for the treatment of a liquid, such as water.

Abstract: The present invention relates generally to glutamine-free cell culture media supplemented with arginine. The invention further concerns the production of recombinant proteins, such as antibodies, in arginine-supplemented glutamine-free mammalian cell culture.

Abstract: A crystalline structure of glutaminyl cyclase (QC) is described. Also described are the methods of preparing the crystalline structure of QC and the methods for identifying candidate inhibitors of QC. In addition, a structural basis for the rational design or identification of new inhibitors that may be used to treat QC-associated disorders is also described.

Abstract: The invention concerns multiparticulate galenic formulations for oral administration and designed for colon targeted delivery of active principles selected from the group comprising enzymes capable of inactivating macrolides and the like, enzymes capable of inactivating quinolones and ?-lactamases.

Abstract: A composition-of-matter for use in water treatment, composed of a water-insoluble matrix and one or more amidohydrolase, such as cyanuric acid amidohydrolase, incorporated in or on the matrix, is disclosed. Also disclosed are devices containing same and methods utilizing same for water treatment. The water treatment is effected by an enzymatically-catalyzed reduction of the concentration of an amide-containing compound, such as cyanuric acid, found in chlorinated water of swimming polls, spas and other similar structures.

Abstract: The object of the present invention is to provide a detection method that can detect an antigen even if the target antigen has a low molecular weight in a simpler, more efficient, and more stable manner and with higher sensitivity. The detection of the antigen is carried out by using a fusion protein comprising a polypeptide containing a VH domain of an antibody; a given protein; a linker peptide; a partner protein having an activity of binding to the protein and capable of detecting binding to the protein; and a polypeptide containing a VL domain of the antibody; in this order or in inverse order to this order, wherein the presence or absence of the binding of the polypeptide containing a VH domain and the polypeptide containing a VL domain to the antigen induces the presence or absence of the binding of the protein and the partner protein.

Abstract: The present invention refers to a recombinant nucleotide sequence which codes upon expression for at least a part of a bifunctional hybrid active-site serine ?-lactamase protein, wherein the ?-lactamase protein is bearing at least one heterologous sequence, wherein in that the hybrid protein is having two functions, the first function is associated with the ?-lactamase portion and the second function is associated with the heterologous sequence having a biological function which is different from the first function.

Abstract: The present disclosure relates to engineered penicillin G acylase (PGA) enzymes having improved properties, polynucleotides encoding such enzymes, compositions including the enzymes, and methods of using the enzymes.

Abstract: The present invention related to a method for crystallizing a CMY-10 being a ?-lactamase with extended-substrate spectrum, a crystal of CMY-10, and a crystal structure of CMY-10. With utilization of three-dimensional structure of CMY-10 protein provided by the present invention, it is possible to develop novel antibiotics or inhibitors that can prevent an emergence of resistance bacteria appeared by plasmidic class C ?-lactamases having extended-substrate specificity.

Abstract: The present invention relates to a 5-substituted hydantoin racemase, which efficiently catalyzes racemization reactions at a high optimum temperature for racemization reactions, DNA coding for the racemase, and processes for producing optically active amino acids.

Abstract: A crystalline structure of glutaminyl cyclase (QC). is described. Also described are the methods of preparing the crystalline structure of QC and the methods for identifying candidate inhibitors of QC. In addition, a structural basis for the rational design or identification of new inhibitors that may be used to treat QC-associated disorders is also described.

Abstract: The present invention provides targeted enzymes that bind to targets better than the corresponding pre-targeted enzymes bind the target under like conditions, methods of making targeted enzymes, methods of using targeted enzymes to treat diseases, and pharmaceutical compositions comprising targeted enzymes.

Abstract: Enzymes with cephalosporin C acylase activity obtained by site-directed, random or “site-saturation” mutagenesis of a native sequence optimised for expression in E. coli.

Abstract: There is described antifungal combination use of known antifungal agents such as the azoles or polyenes in combination with a lipopeptide compound antifungal agent. More particularly, the invention relates to antifungal combination use of azoles such as fluconazole, voriconazole, itraconazole, ketoconazole, miconazole, ER 30346 and SCH 56592; polyenes such as amphotericin B, nystatin, liposomal and lipid forms thereof such as Abelcet, AmBisome and Amphocil; purine or pyrimidine nucleotide inhibitors such as flucytosine; or polyoxins such as nikkomycins, in particular nikkomycin Z or nikkomycin X; other chitin inhibitors; elongation factor inhibitors such as sordarin and analogs thereof; mannan inhibitors such as predamycin, bactericidal/permeability-inducing (BPI) protein products such as XMP.97 or XMP.127; or complex carbohydrate antifungal agents such as CAN-296; with a lipopeptide compound [I] as described herein.

Abstract: The present invention provides a method of producing optically active amino acids from 5-substituted hydantoin by isolating a hydantoinase gene and an N-carbamyl-L-amino acid hydrolase gene involved in an ability to convert 5-substituted hydantoin or N-carbamylamino acid into optically active amino acids from a microorganism of the genus Microbacterium having the above ability and by improving gene amplification and transcriptional and translational activities thereby preparing a recombinant wherein the amount of the desired enzymes produced is increased. The hydantoinase gene is, for example, a DNA encoding for a protein having a hydantoinase activity, which has the nucleotide sequence set forth in SEQ ID NO:1 in the Sequence. The N-carbamyl-L-amino acid hydrolase gene is, for example, a DNA encoding for a protein having an N-carbamyl-L-amino acid hydrolase activity, which has the nucleotide sequence set forth in SEQ ID NO:3 in the Sequence.

Abstract: A tool that can screen bacteria for ?-lactamases against a panel of various antibiotics is desirable. A biosensor incorporating an indicator molecule into ?-lactamases may achieve this purpose, but it requires that the attached indicator molecule must not impair the binding affinity of the protein to a great extent to provide a higher sensitivity. A modified ?-lactamases with a residue on the ?-loop or outside the ?-loop but close to the active site of ?-lactamase being replaced by a reactive residue is developed in this invention.

Abstract: The invention relates to nucleic acid sequence encoding enantioselective amides with an amino acid sequence of SEQ ID NO: 2. The invention also relates to a process for fermentation, comprising a batch and a feed phase, of a microorganism in a fermentation medium, wherein the microorganism expresses a nucleic acid according to the invention and wherein between 0.5 and 50 mg of Zn2+/ml of fermentation medium is fed during the fermentation. The invention also relates to a process for the preparation of enatiomerically enriched carboxylic acid and/or an enatiomerically enriched carboxylic acid amide, in which a mixture of corresponding D- and L-carboxylic acid amides is contacted with a expression product according to the invention in the presence of 0.01 mM–100 mM Zn2+, whereby one of the enantiomers of the carboxylic acid amide is enatiomerically hydrolysed to from corresponding enatiomerically enriched carboxylic acid, while the other enantiomer of the carboxylic acid amide remains unchanged.

Abstract: An n-type MOSFET (NMOS) is implemented on a substrate having an epitaxial layer of strained silicon formed on a layer of silicon germanium. The MOSFET includes first halo regions formed in the strained silicon layer that extent toward the channel region beyond the ends of shallow source and drain extensions. Second halo regions formed in the underlying silicon germanium layer extend toward the channel region beyond the ends of the shallow source and drain extensions and extend deeper into the silicon germanium layer than the shallow source and drain extensions. The p-type dopant of the first and second halo regions slows the high rate of diffusion of the n-type dopant of the shallow source and drain extensions through the silicon germanium toward the channel region. By counteracting the increased diffusion rate of the n-type dopant in this manner, the shallow source and drain extension profiles are maintained and the risk of degradation by short channel effects is reduced.

Abstract: The present invention relates to a chimeric target molecule having an activity which can be regulated or modulated by a binding molecule. The invention also relates to methods of using the chimeric target molecule to detect the presence and/or amount of a desired analyte in a sample. The analyte is a binding molecule, or a competitor of a binding molecule, which binding molecule, upon binding to the target molecule, alters the activity of the target molecule in a detectable way. In one aspect of the invention, a binding molecule binds to the chimeric molecule, inactivating it. An analyte in a test sample competes and/or displaces the binding molecule from the chimera, reactivating it. The reappearance of activity in the presence of the analyte indicates its existence in the test sample existence and amount. Another aspect of the invention relates to a binding molecule which regulates a chimeric target molecule and methods of producing it.

Abstract: This invention relates to isolated nucleic acid fragments encoding aminoacyl-tRNA synthetases and particulary lsoleucyl-, lysyl-, phenylalanyl- and prolyl-tRNA synthetases from Zea mays, Oryza sativa, Glycine max and Tritium aestivum. The invention also relates to the construction of a chimeric gene encoding all or a portion of the aminoacyl-tRNA synthetase, in sense or antisense orientation, wherein expression of the chimeric gene results in production of altered levels of the aminoacyl-tRNA synthetase in a transformed host cell.

Abstract: Electrochemiluminescent-labels and enzyme substrates, which preferably are conjugated, are used in immunoassays and electrochemiluminescence is generated catalytically. In conventional electrochemiluminescence immunoassays, an anti-analyte antibody molecule can give rise to typically 6–8 electrochemiluminescence-active ruthenium atoms, while in the present invention, each enzyme-labeled anti-analyte molecule can give rise to thousands of electrochemiluminescence-active ruthenium atoms per second. An exemplary immunoassay is based on a catalytic process employing ?-lactamase-conjugated anti-analytes which enzymatically hydrolyze electrochemiluminescent-labeled substrates, making them strongly electrochemiluminescent. The electrochemiluminescence signal generated by each anti-analyte molecule (i.e., each analyte molecule) is much greater than with the conventional method. Accordingly, greater sensitivity can be gained in the measurement of low concentrations of a given immunoassay analyte.

Abstract: The invention is in particular related to a method for the selective survival or selective growth of a target cell comprising the steps of: a) contacting the target cell with a conjugate compound A-B, wherein A is a selective antibody or antibody derivative recognizing the target cell and B is a biotic agent able to at least partially inactivate an anti-bios agent, said anti-bios agent is able to inhibit the growth of cells; and b) contacting the target cell with the anti-bios agent. The present invention also relates to said conjugate on its own, a selection medium for cells comprising said conjugate and cells that are selected or recognized using a method or conjugate according to the present invention.

Abstract: There is described antifungal combination use of known antifungal agents such as the azoles or polyenes in combination with a lipopeptide compound antifungal agent. More particularly, the invention relates to antifungal combination use of azols such as fluconazole voriconazole, itraconazole, ketoconazole, miconazole, ER 30346 and SCH 56592; polyenes such as amphotericin B, nystatin, liposomal and lipid forms thereof such as Abelcet, AmBisome and Amphocil; purine or pyrimidine nucleotide inhibitors such as flucytosine; or polyoxins such as nikkomycins, in particular nikkomycin Z or nikkomycin X; other chitin inhibitors; elongation factor inhibitors such as sordarin and analogs thereof; mannan inhibitors such as predamycin, bactericidal/permeability-inducing (BPI) protein products such as XMP.97 or XMP.127; or complex carbohydrate antifungal agents such as CAN-296; with a lipopeptide compound (I) as described herein.

Abstract: The present invention provides a cyclic lipopeptide acylase which may effectively deacylate the acyl side chain of a cyclic lipopeptide compound, specifically FR901379 Substance or its analog thereof shown by the following general formula [I], and a process for production of a cyclic peptide compound which comprises the use of said acylase.

Abstract: The present invention relates to a novel D-hydantoinase from Ochrobactrum anthropi that enantio-selectively hydrolyzes D-hydantoins to their corresponding D-N-carbamoyl-amino acids; nucleic acids that encode for the enzyme; expression vectors including the nucleic acids; and host cells capable of expressing the enzyme.

Abstract: Rec-hydantoinases which may be obtained in more active form by a the process described herein. The invention also relates, inter alia, to a rechydantoinase from the organism Arthrobacter crystallopoietes DSM20117, to nucleic acids which code for such a protein and to vectors containing said nucleic acids and to uses thereof.

Abstract: A process is described for the production of D-&agr;-amino acids by the stereospecific conversion of racemic mixtures of 5-substituted hydantoins using a microorganism transformed with a plasmid which expresses an enzymatic system which converts the hydantoins into the corresponding D-&agr;-amino acids without the requirement for inducers. Also described is a plasmid containing genes encoding the enzymatic system, and a microorganism transformed with the plasmid.

Abstract: Hydantoinase enzymes which are mutants of a previously isolated hydantoinase having the amino acid SEQ. ID. NO. 2. The mutants include amino acid substitutions at positions 95, 154, 180, 251 and/or 255 of the wild type hydantoinase (SEQ. ID. NO. 2). The mutant hydantoinases, like the parent hydantoinase, are used in the production of optically pure amino acids.

Abstract: The present invention relates to a chimeric target molecule having an activity which can be regulated or modulated by a binding molecule. The invention also relates to methods of using the chimeric target molecule to detect the presence and/or amount of a desired analyte in a sample. The analyte is a binding molecule, or a competitor of a binding molecule, which binding molecule, upon binding to the target molecule, alters the activity of the target molecule in a detectable way. In one aspect of the invention, a binding molecule binds to the chimeric molecule, inactivating it. An analyte in a test sample competes and/or displaces the binding molecule from the chimera, reactivating it. The reappearance of activity in the presence of the analyte indicates its existence in the test sample existence and amount. Another aspect of the invention relates to a binding molecule which regulates a chimeric target molecule and methods of producing it.

Abstract: A method for screening a cDNA library by identifying the expressed protein target, comprising:

Abstract: A lactamase enzyme having good stability, capable of hydrolysing an enantiomer of the bicyclic lactam, 2-azabicyclo[2.2.1]hept-5-en-3-one, to give (−) lactam and (+) amino acid, has been found in a strain of Comamonas acidivorans. The enzyme has been isolated and cloned, and its structure identified.

Abstract: The invention discloses a novel thermostable D-hydantoinase, and relates to the nucleic acid sequence, amino acid sequence and vector constructs of the enzyme. The thermostable D-hydantoinase of the invention shows about 45%-70% identity in amino acid sequence with other D-hydantoinases. The thermostable D-hydantoinase of the invention converts 5′-substituted D-hydantoinase to the corresponding N-carbamoyl-D- and/or -L-&agr;/&bgr;-amino acids, and retains at least 50% activity after 30 days at 50° C. In addition, the enzyme activity can also enhanced by certain divalent cations.

Abstract: The present invention provides a cyclic lipopeptide acrylase which may effectively deacylate the acyl side chain of a cyclic lipopeptide compound, specifically FR901379 Substance or its analog thereof shown by the following general formula [I], and a process for production of a cyclic peptide compound which comprises the use of said acylase.