Abstract: A truncated mutant of the 92 kDa gelatinase is disclosed which is catalytically active comparable to the full-length enzyme but, unlike the full-length enzyme, is essentially inactive against insoluble elastin. The truncated mutant preferably comprises residues 107-217 fused to residues 391-443 of the parent molecule. The truncated mutant is useful for treatment of disorders requiring the removal of excess connective tissue.

Abstract: A truncated mutant of the 92 kDa gelatinase is disclosed which is catalytically active comparable to the full-length enzyme but, unlike the full-length enzyme, is essentially inactive against insoluble elastin. The truncated mutant preferably comprises residues 107-217 fused to residues 391-443 of the parent molecule. The truncated mutant is useful for treatment of disorders requiring the removal of excess connective tissue.

Abstract: A novel 54 kDa human macrophage metalloelastase (HME) having elastolytic activity and the cDNA which encodes for this enzyme are disclosed.

Abstract: A unique animal model is disclosed which is useful for studying the role of FGF-9 activity in cardiovascular diseases. To provide this animal model, the FGF-9 gene is disrupted in mice, that is, null mutation in the mouse FGF-9 gene is engineered. This knockout mouse was produced by deleting the sequences immediately downstream of the initiation methionine in exon 1. Analysis of the FGF-9 null embryos demonstrates perinatal lethality with apparent pathology in lung and cardiac tissue.

Abstract: A non-invasive method for the determination of oxidative stress in a patient by urinalysis is disclosed. The method comprises quantifying the level of o,o'-dityrosine in a sample of the urine of said patient and comparing with the corresponding level of said compound in a normal or control sample, whereby a substantially elevated level of said o,o'-dityrosine is indicative of oxidative stress in said patient.

Abstract: Novel inhibitors of retroviral protease, e.g., HIV protease, are provided which are peptides having from about 4 to about 8 amino acid residues and which are substrates for said protease derived from known cleavage sites and modified to contain an internal CH.sub.2 NH bond isostere.

Abstract: A monoclonal antibody which specifically reconizes a receptor that binds to proteins that contain the amino acid sequence Arg-Gly-Asp which on binding said proteins causes the cells to become substantially more phagocytic.

Abstract: A noninvasive method for the determination of oxidative stress in a patient is disclosed. The method comprises quantifying the levels or relative distribution of a pair of compounds, o,o'-dityrosine and o-tyrosine, in a sample of the patient's urine and comparing with the corresponding levels or relative distribution of the compounds in a normal or control sample.

Abstract: Novel short peptides are disclosed which are selected from the group consisting of TAVTQTYGGNSNGEP and fragments thereof containing the minimal sequence TATQTY. These peptides are antithrombotic agents and mediate divalent cation-independent adhesion of platelets to fibronectin.

Abstract: A method is disclosed for modifying the carbohydrate moiety on glycoproteins to facilitate the structural and functional analysis of said glycoproteins such as by NMR spectroscopic analysis and crystallography which comprises treating glycoprotein-secreting mammalian cells having low endomannosidase activity under cell culture maintenance conditions with a glucosidase I inhibitor, and after secretion and purification, subsequent treatment of the active glycoprotein with endoglycosidase H to thereby provide a glycoprotein with a single GlcNAc residue at each glycosylation sequon. The preferred mammalian cells are CHO cells and the preferred glucosidase I inhibitor is N-butyl deoxynojirimycin.

Abstract: A method of inhibiting parasitic activity is disclosed in which the biosynthesis, structure and/or function of the glycosyl phosphatidylinositol (GPI) anchor of said parasite may be affected by incorporating into said GPI anchor selected analogs of myristic acid containing various heteroatoms, substituents and unsaturated bonds, including ester-containing analogs, ketocarbonyl-containing analogs, sulfur-containing analogs, double bond- and triple bond-containing analogs, aromatic moiety-containing analogs, nitrated analogs and halogenated analogs.

Abstract: A method is disclosed for the treatment of hepatitis B virus (HBV) infections which comprises administering to the infected host an N-alkyl derivative of 1,5-dideoxy-1,5-imino-D-glucitol in which the alkyl group contains from 3 to 6 carbon atoms.

Abstract: A method of inhibiting parasitic activity is disclosed in which the biosynthesis, structure and/or function of the glycosyl phosphatidylinositol (GPI) anchor of said parasite may be affected by incorporating into said GPI anchor selected analogs of myristic acid containing various heteroatoms, substituents and unsaturated bonds, including ester-containing analogs, ketocarbonyl-containing analogs, sulfur-containing analogs, double bond- and triple bond-containing analogs, aromatic moiety-containing analogs, nitrated analogs and halogenated analogs.

Abstract: Disclosed are methods of cell surface activation and inhibition that involve the interaction of an inhibitor of matrix metalloprotease known as TIMP-2, with the enzyme, gelatinase-A (GelA). Critical to the methods of the invention is the discovery of a unique TIMP-2 binding site on the surface of the C-terminal domain (GelA-CTD) of the enzyme, which has been determined to be Asp.sup.656, but which can also included other residues in the GelA-CTD domain with which Asp.sup.656 forms a contiguous surface, namely Gly.sup.651, Phe.sup.650, and Tyr.sup.636 Identification of this binding site provides a useful target for the screening of MMP inhibitors and for prognosis and treatment of diseases in which MMPs are implicated. Compounds which are candidate MMP inhibitors can be structured to competitively inhibit cell surface activation.

Abstract: A method of inhibiting parasitic activity is disclosed in which the biosynthesis, structure and/or function of the glycosyl phosphatidylinositol (GPI) anchor of said parasite may be affected by incorporating into said GPI anchor selected analogs of myristic acid containing various heteroatoms, substituents and unsaturated bonds, including ester-containing analogs, ketocarbonyl-containing analogs, sulfur-containing analogs, double bond- and triple bond-containing analogs, aromatic moiety-containing analogs, nitrated analogs and halogenated analogs.

Abstract: A method of inhibiting parasitic activity is disclosed in which the biosynthesis, structure and/or function of the glycosyl phosphatidylinositol (GPI) anchor of said parasite may be affected by incorporating into said GPI anchor selected analogs of myristic acid containing various heteroatoms, substituents and unsaturated bonds, including ester-containing analogs, ketocarbonyl-containing analogs, sulfur-containing analogs, double bond- and triple bond-containing analogs, aromatic moiety-containing analogs, nitrated analogs and halogenated analogs.

Abstract: Novel derivatives of fatty acid analogs that have from one to three heteroatoms in the fatty acid moiety which can be oxygen, sulfur or nitrogen, are disclosed in which the carboxy-terminus has been modified to form various amides, esters, ketones, alcohols, alcohol esters and nitrites thereof, and are useful as substrates for N-myristoyltransferase (NMT) and/or its acyl coenzyme, as anti-viral and anti-fungal agents or pro-drugs of such agents.

Abstract: Novel oxy- and thio-substituted fatty acid analog substrates of myristoylating enzymes are provided which contain an oxygen or sulfur in place of a methylene group in a carbon position from 4 to 13 in the fatty acid chain of a C.sub.13 -C.sub.14 fatty acid or alkyl ester thereof.

Abstract: Novel derivatives of fatty acid analogs that have from one to three heteroatoms in the fatty acid moiety which can be oxygen, sulfur or nitrogen, are disclosed in which the carboxy-terminus has been modified to form various amides, esters, ketones, alcohols, alcohol esters and nitriles thereof, and are useful as substrates for N-myristoyltransferase (NMT) and/or its acyl coenzyme, as anti-viral and anti-fungal agents or pro-drugs of such agents.

Abstract: Novel short peptides are disclosed which are selected from the group consisting of TAVTQTYGGNSNGEP and fragments thereof containing the minimal sequence TAVTQTY. These peptides are antithrombotic agents and mediate divalent cation-independent adhesion of platelets to fibronectin.