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.These compounds are useful as substrates for N-myristoyltransferase (NMT) and/or its acyl coenzyme, and as anti-viral and anti-fungal agents or pro-drugs of such agents. Illustrative of the disclosed compounds are fatty acid amino acid analogs of the structure ##STR1## in which X is the ethyl or t-butyl ester of an amino acid such as Gly, L-Ala, L-Ile, L-Phe, L-Trp, L-Thr or an amide such as NHCH.sub.2 C.sub.6 H.sub.5 or NH(CH.sub.2).sub.2 C.sub.6 H.sub.5.
Abstract: A method is disclosed for inhibiting intimal hyperplasia in a warm-blooded mammal which comprises administering topically at the site and time of a vascular injury induced by arterial intervention in said mammal a small but inhibitorily effective amount of tissue factor pathway inhibitor (TFPI) sufficient to inhibit said intimal hyperplasia.
Type:
Grant
Filed:
September 25, 1996
Date of Patent:
June 22, 1999
Assignee:
Washington University
Inventors:
David M. Brown, Tze-Chein Wun, Roger K. Khouri
Abstract: Disclosed are fibroblast growth factor (FGF) binding and FGF receptor activation, and a method of identifying small molecular weight compounds that interact with FGF to modulate its activity such as, e.g., activators and inhibitors. Illustrative small oligosaccharides, namely di- and tri-saccharides, are shown to be effective modulators of FGF binding and FGF receptor activation.
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.
Type:
Grant
Filed:
July 15, 1993
Date of Patent:
February 16, 1999
Assignee:
Washington University
Inventors:
Robert O. Heuckeroth, Steven P. Adams, Jeffrey I. Gordon
Abstract: A novel transposon useful for sequencing long DNAs is disclosed which comprises a partial sequence of transposon Tn5 with the oligonucleotide primers from phages SP6 and T7 inserted near the opposite ends, respectively, of said transposon Tn5.
Type:
Grant
Filed:
January 14, 1993
Date of Patent:
February 9, 1999
Assignee:
Washington University
Inventors:
Dilip K. Nag, Henry V. Huang, Douglas E. Berg
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.These compounds are useful as substrates for N-myristoyltransferase (NMT) and/or its acyl coenzyme, and as anti-viral and anti-fungal agents or pro-drugs of such agents. Illustrative of the disclosed compounds are fatty acid amino acid analogs of the structure ##STR1## in which x is the ethyl or t-butyl ester of an amino acid such as Gly, L-Ala, L-Ile, L-Phe, L-Trp, L-Thr or an amide such as NHCH.sub.2 C.sub.6 H.sub.5 or NH(CH.sub.2).sub.2 C.sub.6 H.sub.5.
Abstract: A pre-formed anticoagulant heparin/TFPI complex which consists of a weight ratio of at least 1.25 parts of heparin to one part of TFPI and its use in inhibiting blood cogulation.
Abstract: There is disclosed a method of inhibiting fibrin dependent glomerulonephritis which comprises administering to a warm-blooded mammal a heparin/TFPI complex which consists of a weight ratio of at least 1.25 parts of heparin to one part of TFPI.
Abstract: There is disclosed an assay method of screening and identification of anti-amebic drugs which utilizes the ability to inhibit anaerobic growth of a novel bacterial mutant that expresses the EhADH2 gene and which bypasses the conventional need for a parasitic culture. The novel mutant, designated E. coli/EhADH2, is cultured under anaerobic conditions, a predetermined or known quantity of the agent to be tested or target compound is combined with the cell culture, and the combination is then monitored to determine the inhibitory effect upon the anaerobic growth of the E. coli/EhADH2 cell mutant.
Abstract: A method is disclosed for the treatment of Tay-Sachs disease comprising subjecting said cells to a glycolipid inhibitory effective amount of an N-alkyl derivative of 1,5-dideoxy-1,5-imino-D-glucitol in which said alkyl contains from 2-8 carbon atoms.
Type:
Grant
Filed:
January 13, 1997
Date of Patent:
September 1, 1998
Assignee:
Monsanto Company
Inventors:
Frances M. Platt, Gabrielle R. Neises, Raymond A. Dwek, Terry D. Butters
Abstract: A method is disclosed for the in vivo treatment of patients having a lysosomal storage disease with a significant central nervous system (CNS) involvement. Said method comprises administration to said patient a small but storage-inhibitory effective amount of an N-alkyl derivative of a 1,5-iminosugar in which said alkyl group contains from about 2 to about 8 carbon atoms and said 1,5-iminosugar is 1,5-dideoxy-1,5-imino-D-glucitol, or 1,5-dideoxy-1,5-imino-D-galactitol, or an O-acylated pro-drug of said 1,5-iminosugar. In an illustrative example, CNS storage of GM2 ganglioside is inhibited in Tay-Sachs mice by administration of 1,5-(butylimino)-1,5-dideoxy-D-glucitol.
Type:
Grant
Filed:
January 13, 1997
Date of Patent:
August 25, 1998
Assignee:
Monsanto Company
Inventors:
Frances M. Platt, Gabrielle R. Neises, Raymond A. Dwek, Terry D. Butters
Abstract: A method is disclosed for inhibiting the surface expression of glycolipid receptors for bacteria by subjecting bacteria cells to an inhibitory effective amount of an N-alkyl derivative of 1,5-dideoxy-1,5-imino-D-glucitol in which said alkyl contains from 2-8 carbon atoms.
Type:
Grant
Filed:
May 20, 1996
Date of Patent:
July 28, 1998
Assignee:
Monsanto Company
Inventors:
Frances M. Platt, Gabrielle R. Neises, Raymond A. Dwek, Terry D. Butters
Abstract: Novel N-alkyl derivatives of deoxygalactonojirimycin are provided in which said alkyl contains from 3-6 carbon atoms. These novel compounds are useful for selectively inhibiting glycolipid synthesis.
Type:
Grant
Filed:
January 17, 1996
Date of Patent:
July 28, 1998
Assignee:
Monsanto Company
Inventors:
Frances M. Platt, Gabrielle R. Neises, Raymond A. Dwek, Terry D. Butters
Abstract: A method of inhibiting parasitic activity is disclosed in which the biosynthesis, structure and/or function of the glycotyl 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.
Type:
Grant
Filed:
March 18, 1996
Date of Patent:
June 2, 1998
Assignees:
Washington University, Johns Hopkins Univ.
Inventors:
Jeffrey I. Gordon, George W. Gokel, Paul T. Englund
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.
Type:
Grant
Filed:
September 5, 1995
Date of Patent:
May 5, 1998
Assignees:
Washington University, Johns Hopkins University
Inventors:
Jeffrey I. Gordon, George W. Gokel, Paul T. Englund
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.These compounds are useful as substrates for N-myristoyltransferase (NMT) and/or its acyl coenzyme, and as anti-viral and anti-fungal agents or pro-drugs of such agents. Illustrative of the disclosed compounds are fatty acid amino acid analogs of the structure ##STR1## in which X is the ethyl or t-butyl ester of an amino acid such as Gly, L-Ala, L-Ile, L-Phe, L-Trp, L-Thr or an amide such as NHCH.sub.2 C.sub.6 H.sub.5 or NH(CH.sub.2).sub.2 C.sub.6 H.sub.5.
Abstract: Disclosed are fibroblast growth factor (FGF) binding and FGF receptor activation, and a method of identifying small molecular weight compounds that interact with FGF to modulate its activity such as, e.g., activators and inhibitors. Illustrative small oligosaccharides, namely di- and tri-saccharides, are shown to be effective modulators of FGF binding and FGF receptor activation.
Abstract: A diagnostic method and screening test for atherosclerosis and analogous diseases involving activated phagocytes and/or inflammation is provided which comprises determining the presence of p-hydroxyphenylacetaldehyde-lysine in a test sample of a body fluid or tissue at a level which is elevated relative to the level in a normal patient.
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. These compounds are useful as substrates for N-myristoyltransferase (NMT) and/or its acyl coenzyme, and as anti-viral and anti-fungal agents or pro-drugs of such agents. Illustrative of the disclosed compounds are fatty acid amino acid analogs of the structure ##STR1## in which X is the ethyl or t-butyl ester of an amino acid such as Gly, L-Ala, L-Ile, L-Phe, L-Try, L-Thr, or an amide such as NHCH.sub.2 C.sub.6 H.sub.5 or NH(CH.sub.2).sub.2 C.sub.6 H.sub.5.
Abstract: A herpes simplex virus (HSV) mutant, UL41NHB, is disclosed which is deficient in the virion host shutoff (vhs) function. This mutant is shown to be profoundly attenuated in its ability to replicate at the periphery and in the nervous system, and in its ability to reactivate from latency.