Abstract: The present invention relates to the signalling pathways connecting DNA damage, such as that induced by ionizing radiation or alkylating agents, and phosphorylation by tyrosine kinases.

Abstract: The invention is directed to the family of aggrecan degrading metallo proteases (ADMPs) that exhibit the ability to cleave the aggrecan core protein between amino acid residues Glu373-Ala374. The invention encompasses the nucleic acids encoding such enzymes, processes for production of recombinant ADMPs, compositions containing such enzymes, and the use of these enzymes in various assays and for the development of novel inhibitors for use as therapies for diseases involving aggrecanase-mediated degradation of cartilage or other aggrecanase-associated diseases.

Abstract: The present invention provides genes encoding variants of metallo-endopeptidases that have been engineered to be resistant to prolonged boiling while having maintained their enzymatic performance at much lower temperatures. In addition, thermal stability of the metallo-endopeptidases is highly dependent on calcium at concentrations in the mM range. The invention further provides active metallo-endopeptidases variants whose stability depending on calcium concentration can be changed so as to provide metallo-endopeptidases that are calcium dependent or independent. The invention also provides genes that encode boiling-resistant metallo-endopetidases whose stability depending on calcium concentration can be changed. The invention also provides vectors and cells comprising these genes and proteases produced through these genes, vectors and/or cells.

Abstract: The present invention relates to polynucleotide and polypeptide molecules for mouse ztryp1, a novel member of the serine protease family of proteins. The polynucleotides encoding mouse ztryp1 can be used to identify a human ortholog or to create a mouse model associated with human disease states. The present invention also includes methods for producing the protein, uses therefor and antibodies thereto.

Abstract: Novel peptide analogs derived from the native sequences of CAP37 peptides 20-44 and 23-42, and their use as therapeutics against bacterial infections and diseases caused by bacterial infection. The peptide analog includes a serine or threonine substitution at one of the two cysteine residues at positions 26 and 42. Substitutions of the native peptide are also contemplated.

Abstract: This invention relates to novel mutant filamentous fungi which are deficient in the gene for the corresponding aspartic proteinase. These organisms are useful production hosts in the production of heterologous polypeptides such as chymosin.

Abstract: Plasminogen activator acts as an anti-inflammatory agent by inhibiting generation of superoxide anion by a mechanism that is not related to L-arginine, is not dependent on thrombolytic activity, and is not a function of oxygen free radical scavenging. Moreover, in in vivo models of inflammation, treatment with plasminogen activator reduces edema without inhibiting neutrophil infiltration in in vivo models of inflammation.

Abstract: Compounds of the general formula I are provided: and pharmaceutically acceptable salts thereof, wherein, Z is a chemical species or Ri capable of binding at a primary specificity site of a protease; Y is a chemical species reactive to a specific class of protease; each of R2, R3, R5 and R7 is independently selected from the group consisting hydrogen, alkyls, aryls, substituted aryls, alkylaryls and arylalkyls; R4 and R6 are independently selected from the group consisting of: (a) H, alkyl, aryl, arylalkyl, alkylaryl, substituted derivatives thereof, and Ri; (b) —C(O)OH and derivatives thereof, said derivatives selected from the group consisting of —C(O)OQ, —C(O)NRYRZ, —C(O)[NHCHRi(q)C(O)]qOQ, and —C(O)[NHCHRi(q)C(O)]qNRYRZ; and (c) —CHRiNH2 and derivatives thereof, said derivatives selected from the group consisting of —CHRiNHW, —CHRiNHC(O)OQ, —CHRiNHC(O)R, —CHRiNHC(O)NRYRZ, —CHRiNHC(O)[NHCHRi(q

Abstract: The present invention provides a polypeptide of 26 amino acid residues that comprises the minimal ankyrin binding (MAB) domain. The MAB domain is responsible for the interactions between a Na,K-ATPase and ankyrin. The present invention also provides the three dimensional structure of the MAB domain. Also provided by the present invention are methods for modulating the interaction of a Na,K-ATPase and ankyrin.

Abstract: The present invention provides amino acid sequences of peptides that are encoded by genes within the human genome, the protease peptides of the present invention. The present invention specifically provides isolated peptide and nucleic acid molecules, methods of identifying orthologs and paralogs of the protease peptides, and methods of identifying modulators of the protease peptides.

Abstract: Disclosed is a human osteoclast-derived cathepsin (Cathepsin O) polypeptide and DNA(RNA) encoding such cathepsin O polypeptides. Also provided is a procedure for producing such polypeptide by recombinant techniques. The present invention also discloses antibodies, antagonists and inhibitors of such polypeptide which may be used to prevent the action of such polypeptide and therefore may be used therapeutically to treat bone diseases such as osteoporosis and cancers, such as tumor metastases.

Abstract: The invention relates to a process for the preparation of thromboplastin from animal tissue, using an extraction with an aqueous salt solution, followed by separation of tissue material, in order to obtain a thromboplastin containing solution, wherein muscular tissue obtained from mammals or from fish, is used as the animal tissue. The muscular tissue is directly extracted with an aqueous salt solution.

Abstract: The invention concerns the location and characterization of a gene (designated NIM1) that is a key component of the SAR pathway and that in connection with chemical and biological inducers enables induction of SAR gene expression and broad spectrum disease resistance in plants. The invention further concerns transformation vectors and processes for overexpressing the NIM1 gene in plants. The transgenic plants thus created have broad spectrum disease resistance.

Abstract: In accordance with the present invention a novel fibrin polymer structure is disclosed. The novel fibrin polymer structure useful, for example, as a surgical sealant, is comprised of a plurality of discrete, droplets of polymerizing or polymerized fibrin each encapsulated by a “skin” of fibrin polymer. These fibrin-skin encapsulated droplets are applied so as to be built up one upon the other, layer by layer, to form an integral sealant structure. The cumulative effect of the encapsulating skins of those droplets which form the sealant surface is a surface skin which unexpectedly resists cell penetration but enhances cell migration across the surface. The sealant structure of the present invention can be prepared by spray delivery of fibrin polymer forming materials wherein the time required for the materials to commence polymerizing after mixing is less than or equal to the transit time of said materials from the applicator tip to the target surface.

Abstract: The present invention provides amino acid sequences of peptides that are encoded by genes within the human genome, the protease peptides of the present invention. The present invention specifically provides isolated peptide and nucleic acid molecules, methods of identifying orthologs and paralogs of the protease peptides, and methods of identifying modulators of the protease peptides.

Abstract: The invention is directed to the family of aggrecan degrading metallo proteases (ADMPs) that exhibit the ability to cleave the aggrecan core protein between amino acid residues Glu373-Ala374. The invention encompasses the nucleic acids encoding such enzymes, processes for production of recombinant ADMPs, compositions containing such enzymes, and the use of these enzymes in various assays and for the development of novel inhibitors for use as therapies for diseases involving aggrecanase-mediated degradation of cartilage or other aggrecanase-associated diseases.

Abstract: PROTEIN PURIFICATION I The invention relates to processes for preparation of substantially pure antithrombin-III (AT-III), the antithrombin isoforms AT-III&agr; and AT-III&bgr;; and/or histidine-rich glycoprotein (HRGP). The processes comprise separating the said proteins on a cation exchange gel wherein the cation exchanger group is attached to the gel matrix via a linear polymer chain.

Abstract: Methods and compositions that can reduce the symptoms of autism in a human patient comprising administering a physiologically effective amount of one or both of a purified casomorphin inhibitor selected from the group consisting of a casomorphinase and a casomorphin ligand, and a physiologically effective amount of a purified gluteomorphin inhibitor selected from the group consisting of a gluteomorphinase and a gluteomorphin ligand, to a human patient in sufficient quantities to reduce the effects of the autism. In some embodiments, the compositions and methods further comprise a physiologically effective amount of an enkephalin inhibitor, preferably an enkephalinase, and a physiologically effective amount of an endorphin inhibitor, preferably an endorphinase.

Abstract: The invention provides clpL polypeptides and DNA (RNA) encoding clpL polypeptides and methods for producing such polypeptides by recombinant techniques. Also provided are methods for utilizing polypeptides to screen for antibacterial compounds.

Abstract: Novel human polynucleotide and polypeptide sequences are disclosed tat can be used in therapeutic, diagnostic, and pharmacogenomic applications.

Abstract: The present invention relates to a process for removing methionine (Met) residue at N-terminus of proteins specifically. Particularly, the present invention relates to an aminopeptidase which is purified from Bacillus licheniformis removes a methionine residue from N-terminus of peptide and proteins. And the present invention relates to a process for preparing a natural type protein from proteins produced in microorganisms by recombinant DNA technology. Various kinds of natural type proteins such as human growth hormone (HGH) can be prepared massively and easily by the process of the present invention.

Abstract: Members of the serine protease family play a role in carefully controlled processes, such as blood coagulation, fibrinolysis, complement activation, fertilization, and hormone production. These enzymes are also used in a variety of diagnostic, therapeutic, and industrial contexts. Zfaix1 is a new member of the serine protease family.

Abstract: The present invention relates to polynucleotide and polypeptide molecules, and variants thereof, for MAPP, a novel member of the Disintegrin Proteases. The polypeptides, and polynucleotides encoding them, are cell-cell interaction modulating and may be used for delivery and therapeutics. The present invention also includes antibodies to the MAPP polypeptides.

Abstract: Disclosed are nucleic acids encoding aortic carboxypeptidase-related polypeptides, polypeptides encoded by these nucleic acids, and methods of using these nucleic acids and polypeptides.

Abstract: The present invention provides for filariid nematode cysteine protease proteins; to filariid nematode cysteine protease nucleic acid molecules, in particular, Dirofilaria immitis L3 larval cysteine protease nucleic acid molecules and Onchocerca volvulus L3 larval cysteine protease nucleic acid molecules; to antibodies raised against such proteins, and to compounds that inhibit filariid nematode cysteine protease activity. The present invention also includes methods to obtain such proteins, nucleic acid molecules, antibodies and/or inhibitors. The present invention also includes therapeutic compositions comprising such proteins, nucleic acid molecules, antibodies and/or inhibitors, and the use of such compositions to protect an animal from disease caused by parasitic helminths.

Abstract: A method for measuring protease such as matrix metalloproteinase which comprising steps of (1) bringing a biological sample such as protease-containing tissue slices and tissue extracts into contact with a thin membrane which comprises a protease substrate and a hardening agent and is formed on a surface of a support; and (2) detecting the trace of digestion formed on the thin membrane by the action of protease with the naked eyes or under a microscope, and a thin membrane used for said method.

Abstract: New forms of ecarin, a procoagulant protein from Echis carinatus venom, are described, as are polynucleotides encoding the new proteins, methods for production of the new proteins, and methods for activation of prothrombin using the new proteins. The new ecarins comprise a serine at position 396 of the protein. The new proteins may be used for activation of prothrombin, and are particularly useful for the production of recombinant thrombin.

Abstract: The present invention relates to a 35 kDa enzyme exhibiting aminopeptidase activity which is derived from a fungal microorganism, a DNA construct comprising a DNA sequence encoding said enzyme, a recombinant expression vector comprising said DNA construct, and a cell comprising said DNA sequence. The present invention also provides a method for producing said enzyme exhibiting aminopeptidase activity, and an enzyme preparation comprising said enzyme, a bread-improving or dough-improving composition comprising the aminopeptidase of the invention. Finally the invention relates to the use of said enzyme exhibiting aminopeptidase activity or enzyme preparations or compositions thereof.

Abstract: A method for treating various diseases and conditions that are dependent on activated &agr;2 macroglobulin in the blood and extravascular tissue is disclosed. The method comprises orally administering a therapeutically effective amount of protease to a mammal to increase the amount of activated &agr;2 macroglobulin, which in turn enhances the clearance of TNF-&agr;, leptin, and &bgr;-amyloid while enhancing delivery of TGF-&bgr;. The protease may be any pharmaceutically acceptable protease, and preferably is of microbial and/or plant origin, given singly or in combination with vitamins, minerals, antioxidants, bioflavonoids, proanthocyanidins, herbs, herbal extracts, plant and animal concentrates, and non-prescription analgesics. The microbial protease is preferably administered in a total daily dosage of at least 100,000 HUT (or equivalent biological activity). The plant protease component is preferably administered in a total daily dosage of at least 50,000 PU (or equivalent biological activity).

Abstract: Methods and compositions are provided for treating a host suffering from a disease associated with the presence of a pathogenic microorganism. In the subject methods, a pharmaceutical formulation comprising an agent that at least reduces the amount of polyphosphate in said microorganism is administered to said host. The subject methods and compositions find use in the treatment of a variety of disease conditions.

Abstract: The present invention relates to the identification and purification of a herpes protease and a nucleic acid segment coding for two proteins. The first protein is the herpes protease which is able to cleave itself and also cleave the second protein. This protease is required for the assembly of the herpes virus capsid, therefore is essential for replication. The second protein has previously been designated as the family of proteins in viral infected cells, ICP35. The protease and its substrates are encoded by overlapping nucleic acid segments. This invention also relates to a promoter sequence for the second protein. Methods are presented of producing a viral protease, screening a protease inhibitor which may be used in a drug designed for the treatment of herpes disease, methods for treating herpes and other viral infections wherein the virus employs a protease substantially similar to the herpes protease, for capsid production.

Abstract: A method for the production and secretion of proteins with hirudin activity in an eukaryotic host organism is provided. There are also provided hybrid vectors comprising a DNA sequence encoding a signal peptide upstream of and in reading frame with the structural gene for desulphatohirudin, and eukaryotic host organisms transformed with said hybrid vectors.

Abstract: The present invention relates to flea serine protease proteins and flea cysteine protease proteins; to flea serine protease and cysteine protease nucleic acid molecules, including those that encode such proteins; to antibodies raised against such proteins; and to compounds that inhibit flea serine protease and/or cysteine protease activities. The present invention also includes methods to obtain such proteins, nucleic acid molecules, antibodies, and inhibitors. Also included in the present invention are therapeutic compositions comprising such proteins, nucleic acid molecules, antibodies, and/or inhibitors as well as the use of such therapeutic compositions to protect a host animal from flea infestation.

Abstract: Members of a novel family of polypeptides, the KUZ family, are metalloproteases involved in neuronal partitioning and neuronal development. The invention provides KUZ poylpeptides, antibodies that bind the KUZ polypeptides, KUZ encoding nucleic acids, methods for identifying cells expressing the KUZ polypeptides, methods of identifying ligands that bind to the subject proteins and methods of blocking KUZ polypeptide/ligand interactions.

Abstract: Compositions and methods for the therapy and diagnosis of cancer, such as prostate cancer, are disclosed. Compositions may comprise one or more prostate tumor proteins, immunogenic portions thereof, or polynucleotides that encode such portions. Alternatively, a therapeutic composition may comprise an antigen presenting cell that expresses a prostate tumor protein, or a T cell that is specific for cells expressing such a protein. Such compositions may be used, for example, for the prevention and treatment of diseases such as prostate cancer. Diagnostic methods based on detecting a prostate tumor protein, or mRNA encoding such a protein, in a sample are also provided.

Abstract: The present invention relates to a novel t-PALP protein which is a member of the serine protease family. In particular, isolated nucleic acid molecules are provided encoding the human t-PALP protein. t-PALP polypeptides are also provided as are vectors, host cells and recombinant methods for producing the same. The invention further relates to screening methods for identifying agonists and antagonists of t-PALP activity. Also provided are diagnostic methods for detecting circulatory system-related disorders and therapeutic methods for treating circulatory system-related disorders.

Abstract: Disclosed are mammalian thromboplastin reagents and methods for preparing such reagents. The thromboplastin reagents are suitable for use in prothrombin-time (PT) assays, and offer improved sensitivities with acceptable PT-normal times. Contaminating proteins—particularly plasma clotting factors—are separated from a thromboplastin solution by a membrane permeation protocol, in which the thromboplastin solution is exposed to a semipermeable membrane and clotting factors are allowed to pass from the thromboplastin solution through the membrane, while Tissue Factor is retained in the thromboplastin solution. In a preferred method, one or more contaminating clotting factors are separated by diafiltration from a NaCl/Na3Citrate thromboplastin extract of mammalian tissue, and the purified thromboplastin extract is combined with Ca++ ions to form a thromboplastin reagent.

Abstract: Disclosed is a human osteoclast-derived cathepsin (Cathepsin O) polypeptide and DNA(RNA) encoding such cathepsin O polypeptides. Also provided is a procedure for producing such polypeptide by recombinant techniques. The present invention also discloses antibodies, antagonists and inhibitors of such polypeptide which may be used to prevent the action of such polypeptide and therefore may be used therapeutically to treat bone diseases such as osteoporosis and cancers, such as tumor metastases.

Abstract: Disclosed is a human osteoclast-derived cathepsin (Cathepsin O) polypeptide and DNA(RNA) encoding such cathepsin O polypeptides. Also provided is a procedure for producing such polypeptide by recombinant techniques. The present invention also discloses antibodies, antagonists and inhibitors of such polypeptide which may be used to prevent the action of such polypeptide and therefore may be used therapeutically to treat bone diseases such as osteoporosis and cancers, such as tumor metastases.

Abstract: The present invention relates generally to a method of modulating cellular activity and agents useful for same. More particularly, the present invention contemplates a method of modulating endothelial cell activity and even more particularly endothelial cell adhesion molecule expression. Most particularly, the present invention provides a method of treating coronary heart disease by preventing or reducing endothelial cell adhesion molecule expression.

Abstract: The present invention provides a human serine carboxypeptidase (CPEPT) and polynucleotides which identify and encode CPEPT. The invention also provides expression vectors, host cells, agonists, antibodies, and antagonists. The invention also provides methods for treating disorders associated with expression of CPEPT.

Abstract: An alkaline protease having the following properties; a gene encoding the same; a microorganism producing the same; and washing compositions containing the same; (i) acting over a broad pH value range of 4 to 13 and achieving, at pH 6 to 12, 80% or more the activity at the optimum pH value; (ii) when treated at 40° C. for 30 minutes, being stable over a pH value range of 6 to 11; (iii) having an isoelectric point of about 8.9 to 9.1; and (iv) having casein digesting activity that is not inhibited by oleic acid. The alkaline protease of the present invention is highly stable to various surface active agents and fatty acids, and exhibits high stability to oxidizing agents, and is therefore useful as an enzyme to be used in detergents for automatic dishwashers and laundry detergents, both containing bleaching components.

Abstract: Rev-caspases comprising a primary product in which the small subunit is N-terminal to the large subunit are provided. Rev-caspases are used for screening and identifying caspase inhibitors and enhancers. Rev-caspase genes can be delivered to cells for gene therapy.

Abstract: The present invention relates to a novel t-PALP protein which is a member of the serine protease family. In particular, isolated nucleic acid molecules are provided encoding the human t-PALP protein. t-PALP polypeptides are also provided as are vectors, host cells and recombinant methods for producing the same. The invention further relates to screening methods for identifying agonists and antagonists of t-PALP activity. Also provided are diagnostic methods for detecting circulatory system-related disorders and therapeutic methods for treating circulatory system-related disorders.

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.

Abstract: The present invention provides amino acid sequences of peptides that are encoded by genes within the human genome, the protease peptides of the present invention. The present invention specifically provides isolated peptide and nucleic acid molecules, methods of identifying orthologs and paralogs of the protease peptides, and methods of identifying modulators of the protease peptides.

Abstract: The present invention provides a DNA encoding a novel extracellular serine protease termed Tumor Antigen Derived Gene-14 (TADG-14) which is overexpressed in ovarian, breast and colon carcinoma samples. Also provided are vector and host cells capable of expressing the DNA of the present invention, as well as the uses of the DNA and protein of the present invention.

Abstract: Mouse mASP1 polypeptides and polynucleotides and method for producing such polypeptides by recombinant techniques are disclosed. Also disclosed are methods for screening for compounds that either agonize or antagonize mouse mASP1. Such compounds are expected to be useful in treatment of human diseases, including, but not limited to: Alzheimer's disease, cancer, and prohormone processing.

Abstract: A hyperthermostable protease having the amino acid sequence represented by the SEQ ID NO:1 of the Sequence Listing or a sequence derived therefrom by deletion, substitution, insertion or addition of one to several amino acid residues, a gene encoding the hyperthermostable protease, and a process for preparing the protease, aiming at providing by genetic engineering techniques a hyperthermophile protease which is advantageous for industrial use.

Abstract: A method, and DNA constructs useful therein, is provided for producing plasminogen activator in bacteria. Particular constructs are provided comprising a coding sequence for tissue plasminogen activator and the leader peptide thereof, which is used to transform E. coli to produce protein having activity of tissue plasminogen activator.