Of Side Chain Or Sulfur Containing Group Patents (Class 530/336)
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Patent number: 6770436Abstract: Radiation-activated catalysts (RACs), autocatalytic reactions, and protective groups are employed to achieve a highly sensitive, high resolution, radiation directed combinatorial synthesis of pattern arrays of diverse polymers. When irradiated, RACs produce catalysts that can react with enhancers, such as those involved in autocatalytic reactions. The autocatalytic reactions produce at least one product that removes protecting groups from synthesis intermediates. This invention has a wide variety of applications and is particularly useful for the solid phase combinatorial synthesis of polymers.Type: GrantFiled: May 25, 2000Date of Patent: August 3, 2004Assignee: Affymetrix, Inc.Inventors: Jody E. Beecher, Martin J. Goldberg, Glenn H. McGall
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Patent number: 6767718Abstract: Novel cyclodepsipeptide intermediates have been prepared from the A21978 complex and used to synthesize new lipodepsipeptide antibiotics. The three intermediates can be readily derivatized to give new families of antibiotics that have potent antibacterial activity against gram positive bacteria.Type: GrantFiled: May 10, 2002Date of Patent: July 27, 2004Assignee: BioSource Pharm, Inc.Inventors: Richard A. Leese, William V. Curran, Donald B. Borders
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Patent number: 6762282Abstract: A method for producing a S-nitrosylated species is provided. The method comprises: (a) providing a deoxygenated, alkaline aqueous solution comprising a thiol and a nitrite-bearing species; (b) acidifying the solution by adding acid to the solution while concurrently mixing the solution (e.g., by vigorously stirring the solution) to produce the S-nitrosylated species; and (c) isolating the S-nitrosylated species. The nitrite-bearing species can be, for example, an inorganic nitrite, such as an alkali metal nitrite, or an organic nitrite, such as an alkyl nitrite (e.g., ethyl nitrite, amyl nitrite, isobutyl nitrite or t-butyl nitrite). The thiol is preferably a thiol-containing polysaccharide, a thiol-containing lipoprotein, a thiol-containing amino acid or a thiol-containing protein, and more preferably a thiol-containing polysaccharide such as thiolated cyclodextrin. In many preferred embodiments, the S-nitrosylated species is insoluble in the acidified solution, precipitating upon formation.Type: GrantFiled: May 13, 2003Date of Patent: July 13, 2004Assignee: SciMed Life Systems, Inc.Inventors: Robert A. Herrmann, David Knapp
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Patent number: 6747009Abstract: The invention relates to peptidomimetic compounds with formula wherein Z═CH2 and Y═CH2, or Z═O and Y═O═O, which are novel analogs of glutathion and are inhibitors of glutathione S-transferase, in particular of GST P1-1. Such inhibition has beneficial effects in therapy against cancer. In particular compounds in which R3 is H, R4 is benzyl and R5 is phenyl are stable towards &ggr;GT activity and are selective for GST P1-1.Type: GrantFiled: September 19, 2002Date of Patent: June 8, 2004Assignee: Universiteit LeidenInventors: Danny Burg, Gerard Johan Mulder
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Patent number: 6703480Abstract: Novel peptide dimers are provided that bind and activate the erythropoietin receptor (EPO-R) or otherwise act as an EPO agonist. The novel compounds have a first peptide chain R1 and a second peptide chain R2, wherein R1 and R2 may be the same or different, and are linked through a linking moiety. R1 is approximately 10 to 40 amino acid residues in length and comprises the sequence X3X4X5GPX6TX7X8X9 (SEQ ID NO: 1) wherein X3 is C or Hoc, X4 is R, H, L or W, X5 is M, F, I or nor-leucine (J), X6 is any one of the 20 genetically coded L-amino acids or J, X7 is W, 1-naphthylalanine (B) or 2-naphthylalanine (U), X8 is D, E, 1, L or V, and X9 is C or Hoc. Similarly, R2 comprises the sequence X′3X′4X′5GPX′6TX′7X′8X′9 (SEQ ID NO: 2) wherein X′3 is C or Hoc, X′4 is R, H, L or W, X′5 is M, F, I or J, X′6 is any one of the 20 genetically coded L-amino acids or J, X′7 is W, B or U, X8′ is D, E, I, L or V, and X′9 is C or Hoc.Type: GrantFiled: November 24, 1999Date of Patent: March 9, 2004Inventor: Palani Balu
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Patent number: 6605299Abstract: A compound comprised of a hydrophilic polymer covalently yet reversibly linked to a amine-containing ligand through a dithiobenzyl linkage is described.Type: GrantFiled: October 15, 2001Date of Patent: August 12, 2003Assignee: Alza CorporationInventor: Samuel Zalipsky
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Patent number: 6600016Abstract: Multifunctionalized support resin for the solid phase synthesis of combinatorial libraries is disclosed. The support resin comprises a resin backbone to which is attached a template containing at least two more attachment points which carry mutiple functionalized benzyl-type linkers. Each linker displays differing chemical stability under cleavage conditions so that products can be selectively and sequentially cleaved and separated from the reaction vessel. The linkers are independently different benzyl-type moieties, and each product synthesized on the linkers may have a different chemical structure. The support resin may further comprise an additional linker which is directly attached to the resin backbone. This linker can benzyl-type linkers or other traditional cleavable-linkers. The invention is further directed to a method for the production of mutiple combinatorial libraries in a simultaneous fashion utilizing the above described support resin.Type: GrantFiled: August 24, 1999Date of Patent: July 29, 2003Assignee: Advanced Syntech LLCInventors: Eugene Campian, Boliang Lu, Jinfang Zhang
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Patent number: 6566495Abstract: 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.Type: GrantFiled: December 17, 1999Date of Patent: May 20, 2003Assignee: Affymetrix, Inc.Inventors: Stephen P. A. Fodor, Lubert Stryer, J. Leighton Read, Michael C. Pirrung
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Patent number: 6562944Abstract: Disclosed is an improved method for preparing an activated carboxylic acid in the form of a pentafluorophenyl ester, an improved method for making a carboxamide from a pentaflourophenyl ester, and a carboxamide and carboxamide library prepared using both of these methods.Type: GrantFiled: March 22, 2000Date of Patent: May 13, 2003Assignee: Lexicon PharmaceuticalsInventors: Hartmuth C. Kolb, Qun Sun
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Patent number: 6509189Abstract: The presention invention relates to the discovery, identification and characterization of nucleotides that encode Ob receptor (ObR), a receptor protein that participates in mammalian body weight regulation. The invention encompasses obR nucleotides, host cell expression systems, ObR proteins, fusion proteins, polypeptides and peptides, antibodies to the receptor, transgenic animals that express an obR transgene, or recombinant knock-out animals that do not express the ObR, antagonists and agonists of the receptor, and other compounds that modulate obR gene expression or ObR activity that can be used for diagnosis, drug screening, clinical trial monitoring, and/or the treatment of body weight disorders, including but not limited to obesity, cachexia and anorexia.Type: GrantFiled: December 11, 1995Date of Patent: January 21, 2003Assignee: Millennium Pharmaceuticals, Inc.Inventors: Louis Anthony Tartaglia, Robert I. Tepper, Janice A. Culpepper
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Patent number: 6504005Abstract: Disclosed are conjugates of a polypeptide or oligopeptide with a low molecular weight lipophilic compound, the peptide and lipophilic group being covalently linked to one another either directly or via a connecting element, with the exception of (a) conjugates in which the peptide component consists of hirudin or peptide structurally derived from hirudin or a peptide derivative with hirudin-like properties, and (b) conjugates whose peptide component has been hydrophobically modified during their biosynthesis.Type: GrantFiled: February 5, 1999Date of Patent: January 7, 2003Assignee: Yeda Research and Development Co. Ltd.Inventors: Matityahu Fridkin, Yoram Shechter, Eytan Gershonov
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Patent number: 6492491Abstract: The invention relates to novel peptides synthesized according a method utilizing the hypusine reagent: wherein: Q1 Q2 and Q3 may be the same or different and are amino protective groups, provided that Q3 is orthogonal to Q1 and Q2; and Z is a hydroxy protective group, as well as improved methods of peptide synthesis wherein the above-described hypusine reagent is employed to prepare novel hypusine-containing peptides.Type: GrantFiled: March 6, 2000Date of Patent: December 10, 2002Assignee: University of Florida Research FoundationInventor: Raymond J. Bergeron, Jr.
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Patent number: 6458923Abstract: The substitution of the L-Pro at the 7-position of the peptide hormone bradykinin or other substituted analogs of bradykinin with an isoquinoline derivative which converts bradykinin agonists into bradykinin antagonists. The invention further includes the novel 7-position modified bradykinin antagonists which increase enzyme resistance, antagonist potency, and/or specificity of the new bradykinin antagonists. The analogs produced are useful in treating conditions and diseases of a mammal and human in which an excess of bradykinin or related kinins are produced or injected as by insect bites.Type: GrantFiled: September 12, 1994Date of Patent: October 1, 2002Assignee: Scios Inc.Inventor: Donald James Kyle
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Patent number: 6426184Abstract: This invention provides method and apparatus for performing chemical and biochemical reactions in solution using in situ generated photo-products as reagent or co-reagent. Specifically, the method and apparatus of the present invention have applications in parallel synthesis of molecular sequence arrays on solid surfaces.Type: GrantFiled: February 10, 1999Date of Patent: July 30, 2002Assignee: The Regents of the University of MichiganInventors: Xiaolian Gao, Xiaochuan Zhou, Erdogan Gulari
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Patent number: 6417347Abstract: A method for producing a S-nitrosylated species is provided. The method comprises: (a) providing a deoxygenated, alkaline aqueous solution comprising a thiol and a nitrite-bearing species; (b) acidifying the solution by adding acid to the solution while concurrently mixing the solution (e.g., by vigorously stirring the solution) to produce the S-nitrosylated species; and (c) isolating the S-nitrosylated species. The nitrite-bearing species can be, for example, an inorganic nitrite, such as an alkali metal nitrite, or an organic nitrite, such as an alkyl nitrite (e.g., ethyl nitrite, amyl nitrite, isobutyl nitrite or t-butyl nitrite). The thiol is preferably a thiol-containing polysaccharide, a thiol-containing lipoprotein, a thiol-containing amino acid or a thiol-containing protein, and more preferably a thiol-containing polysaccharide such as thiolated cyclodextrin. In many preferred embodiments, the S-nitrosylated species is insoluble in the acidified solution, precipitating upon formation.Type: GrantFiled: August 24, 2000Date of Patent: July 9, 2002Assignee: Scimed Life Systems, Inc.Inventors: Robert A. Herrmann, David Knapp
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Patent number: 6380358Abstract: Trisubstituted N-protected guanidines and methods for use as guanidinylating reagents to yield N-protected guanidine derivatives.Type: GrantFiled: December 1, 1999Date of Patent: April 30, 2002Assignee: The Regents of the University of CaliforniaInventors: Murray Goodman, Konrad Feichtinger, Todd T. Romoff
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Patent number: 6376649Abstract: Methods for the synthesis of &agr;-hydroxy-&bgr;-amino acid and amide derivatives and &agr;-ketoamide derivatives and novel derivatives made by these methods are provided. These methods involve reacting a N-terminally blocked (protected) aminoaldehyde with an isonitrile and a carboxylic acid to give an amino-&agr;-acyloxy carboxamide. The acyloxy group may be removed to give the derivative. Alternatively the protecting group is removed and acyl shift occurs to give the derivative. These derivatives are useful in the synthesis of compounds such as peptidyl &agr;-ketoamides and &agr;-hydroxy-&bgr;-carboxylic acid and amide derivatives. Certain of these compounds have been reported to have activity as inhibitors of proteases, such as serine proteases and cysteine proteases.Type: GrantFiled: December 18, 1998Date of Patent: April 23, 2002Assignee: Corvas International, Inc.Inventors: Joseph E. Semple, Odile E. Levy
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Patent number: 6365179Abstract: Conjugates of a hydrophobic moiety, such as a lipid, linked through a cleavable dithiobenzyl linkage to a therapeutic agent are described. The dithiobenzyl linkage is susceptible to cleavage by mild thiolysis, resulting in release of the therapeutic agent in its original form. The linkage is stable under nonreducing conditions. The conjugate can be incorporated into liposomes for administration in vivo and release of the therapeutic agent in response to endogeneous in vivo reducing conditions or in response to administration of an exogeneous reducing agent.Type: GrantFiled: April 21, 2000Date of Patent: April 2, 2002Assignee: ALZA CorporationInventors: Samuel Zalipsky, Alberto A. Gabizon
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Patent number: 6346601Abstract: A procedure for obtaining the somatostatin analog, octreotide by means of solid phase synthesis on polymer supports and by intervention of protector groups of the Fmoc/tBu type. It includes construction of the seven amino acid, Boc-D-Phe-Cys(Trt)-Phe-D-Trp-Lys(Boc)Thr(tBu)-Cys(Trt)-Cl-trityl-R linear peptide, in which R is a polymer; treatment of the resulting peptidyl-resin with acid, for detachment of the peptide from the resin; cycling the linear structure obtained by reaction with iodine before or after incorporation of the threoninol residue into the terminal carboxy end; incorporating the threoninol residue in solution upon the seven amino acid protected peptide with or without the disulfide bridge formed; and removing the protections at the N-terminus and at the side chains with a treatment with 70-95% TFA in presence of scavengers to obtain octreotide.Type: GrantFiled: January 29, 1999Date of Patent: February 12, 2002Assignee: Lipotec S.A.Inventors: Berta Ponsati Obiols, Gemma Jodas Farres, Marc Canas Poblet, Francisco Javier Clemente Rodriguez
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Patent number: 6342244Abstract: A compound comprised of a hydrophilic polymer covalently yet reversibly linked to a amine-containing ligand through a dithiobenzyl linkage is described.Type: GrantFiled: April 21, 2000Date of Patent: January 29, 2002Assignee: Alza CorporationInventor: Samuel Zalipsky
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Patent number: 6287787Abstract: Dimeric oligopeptide mixture sets, their synthesis and use in determining the sequence of an oligopeptide dimer ligand that optimally binds to a receptor are disclosed. A dimeric oligopeptide mixture set has two oligopeptide portions bonded together by a disulfide bond. Each oligopeptide of a first oligopeptide portion has the same number of 3 to about 10 residues including an oxidized mercaptan-containing residue that forms part of the disulfide bond and an amino acid residue sequence that includes at least one of at least six residues in addition to the oxidized mercaptan-containing residue at the same one or more predetermined positions of the oligopeptide chain. The second portion has an oligopeptide chain having a length of 4 to about 10 residues, including an oxidized mercaptan-containing residue that forms part of the disulfide bond.Type: GrantFiled: November 24, 1993Date of Patent: September 11, 2001Assignee: Torrey Pines Institute for Molecular StudiesInventors: Richard A. Houghten, Clemencia Pinilla
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Patent number: 6288036Abstract: The substitution of the L-Pro at the 7-position with D-Phe or D-Tic and substitution of the L-Phe at the 8-position with hydroxyproline ethers and thioethers of the peptide hormone bradykinin and other additional substituted analogs of bradykinin converts bradykinin agonists into bradykinin antagonists. The invention further includes additional modifications at other positions within the novel 7- and 8-position modified bradykinin antagonists, which increase enzyme resistance, antagonist potency, and/or specificity of the new bradykinin antagonists. The analogs produced are useful in treating conditions and diseases of a mammal and human in which an excess of bradykinin or related kinins are produced or injected as by insect bites.Type: GrantFiled: December 16, 1993Date of Patent: September 11, 2001Assignee: Scios Inc.Inventors: Donald James Kyle, Roger Neal Hiner
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Patent number: 6277958Abstract: 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.Type: GrantFiled: November 27, 1998Date of Patent: August 21, 2001Inventor: Saburho Aimoto
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Patent number: 6248564Abstract: Methods of generating a conjugate of MHC class I molecule and a compound via a cysteine residue engineered into the &bgr;2-M subunit. Also featured are uses of the conjugates.Type: GrantFiled: August 29, 1997Date of Patent: June 19, 2001Assignee: Harvard UniversityInventors: Jürgen B. Walter, David N. Garboczi
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Patent number: 6242565Abstract: A method for preparing a peptide derivative of formula (I) or a salt thereof: which method comprises the steps of removing two MBzl groups from a compound of formula (II) or a salt thereof: wherein MBzl represents a 4-methoxybenzyl group which serves as a protective group for a thiol group, and R1 and R2 represent hydrogen or a protective group for Trp or Arg respectively; and subsequently oxidizing in an aqueous medium having a pH from 4 to 6 to form an intramolecular disulphide bond; intermediates useful for preparing the compounds of formula (I) and preparation of the intermediates.Type: GrantFiled: August 5, 1998Date of Patent: June 5, 2001Assignee: TT Pharmaceuticals, Inc.Inventors: Satoshi Kishida, Akihiro Nakanishi, Hitoshi Kimura
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Patent number: 6225480Abstract: The present invention relates to a linker shown by the following formula (I): X—SO2—R1—(A)m—R2 (I) wherein R1 is a group of the formula (A): [wherein R3, R4 and R5 are the same or different hydrogen, etc], etc, R2 is a group which can form a chemical bond to a resin which may be protected by a conventional protective group, A is lower alkylene, etc, X is a leaving group, and m is an integer of 0 or 1, with proviso that A is (C2-C6)alkylene, and m is an integer of 1, when R1 is a group of the formula (A).Type: GrantFiled: June 30, 1999Date of Patent: May 1, 2001Assignee: Fujisawa Pharmaceutical Co., Ltd.Inventors: Akito Tanaka, Hideo Tsutsumi
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Patent number: 6126916Abstract: Novel metal binding ligands are disclosed that may be coupled to peptides for use in methods of diagnosis and therapy. Peptides containing the ligands are produced using a method wherein ligand introduction or cyclization can be conducted at any point during the synthesis of the peptide. Such peptide derivatives are readily labeled with radiometals, such as isotopes of rhenium or technetium, while retaining their ability to tightly bind specific peptide receptors.Type: GrantFiled: July 11, 1997Date of Patent: October 3, 2000Assignee: Immunomedics, Inc.Inventors: William J. McBride, Gary L. Griffiths
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Patent number: 6031073Abstract: This invention relates generally to cyclic polypeptides comprising a thioether linkage and methods for their preparation. More particularly, this invention relates to halogenated polypeptides having at least one haloalanine-like amino acid, and methods for their preparation which involve converting the hydroxyl group (i.e., --OH) of a serine-like amino acid to a halo group (i.e., --X where X is Cl, Br, or I) with the aid of a phosphorus-based halogenation reagent such as a triphenylphosphine dihalide (i.e., (C.sub.6 H.sub.5).sub.3 PX.sub.2, wherein X is Cl, Br, or I), a triphenylphosphite dihalide (i.e., (C.sub.6 H.sub.5 O).sub.3 PX.sub.2, wherein X is Cl, Br, or I), or a mixture of triphenylphosphine or triphenylphosphite with a halohydrocarbon (i.e., "halo-conversion").Type: GrantFiled: November 19, 1997Date of Patent: February 29, 2000Assignee: La Jolla Pharmaceutical CompanyInventor: Lin Yu
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Patent number: 6028110Abstract: A pharmaceutical or veterinary composition comprising a compound of formula I ##STR1## wherein X is a --CO.sub.2 H group and R.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.5 are as defined in the specification, or a salt, hydrate or solvate thereof, and a pharmaceutically or veterinarily acceptable excipient or carrier. A method of treatment of diseases or conditions mediated by MMPs in mammals, such as rheumatoid arthritis, osteoarthritis, periodontitis, gingivitis, corneal ulceration or tumour invasion by secondary means, by administering to the mammal an effective amount of the composition.Type: GrantFiled: November 22, 1996Date of Patent: February 22, 2000Assignee: British Biotech Pharmaceuticals Ltd.Inventors: Andrew Miller, Raymond Paul Beckett, Fionna Mitchell Martin, Mark Whittaker
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Patent number: 6013764Abstract: The invention relates to improved liquid phase processes for the preparation of the 21 residue protein component, (Lys-Leu.sub.4).sub.4 -Lys, of the pulmonary surfactant KL-4. These process are amenable to large scale synthesis and one process employs a method of saponifying an ester which reduces the inherent racemization of the .alpha.-carbon.Type: GrantFiled: June 25, 1997Date of Patent: January 11, 2000Assignee: Ortho Pharmaceutical Corp.Inventors: Ahmed F. Abdel-Magid, Urs Eggmann, Cynthia Anne Maryanoff, Adrian Thaler, Frank J. Villani
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Patent number: 5998580Abstract: Disclosed is a method for preparing a photosensitive peptide which is capable of being activated or deactivated in a biological system, including the steps of: (a) providing an amino acid including a photolabile molecule; and (b) incorporating the amino acid into a peptide during synthesis, wherein incorporation of the amino acid into the peptide produces a photosensitive peptide. Also disclosed is a method of introducing a photosensitive cleavage site into a synthetic peptide, including synthesizing a synthetic peptide having at least one photolabile amino acid, wherein the photolabile amino acid is positioned within the synthetic peptide so that upon irradiation the synthetic peptide is cleaved.Type: GrantFiled: October 13, 1995Date of Patent: December 7, 1999Inventors: Frederick F. Fay, Robert Carraway, Mitsuo Ikebe, Jeffrey Walker
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Patent number: 5990278Abstract: The invention relates to a carbamide of the general formulaR.sub.1 --CO--NH--C(R.sub.2)(R.sub.3)--X--Ywhich is protected by a temporary protective group and whereinR.sub.1 --CO means a carbonyl residue which can be provided as a unit for the chain of a peptide, and can have one or a plurality of amino acid residues;R2 and R3 mean resides of the carbamide which do not participate in their function, whereby R2 and R3 can be identical or different, but are different when one of the two residues means a hydrogen atom;X means an oxygen atom or a sulphur atom, andY means a protective group for X.The invention further relates to a process for producing the protected carbamide and to utilisation of the protected carbamide.The protected carbamide according to the invention can also be linked to a carrier material.Type: GrantFiled: March 3, 1997Date of Patent: November 23, 1999Inventors: Stefen Hoffmann, Ronald Frank
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Patent number: 5962640Abstract: The present invention provides a novel dipeptide compound or pharmaceutically acceptable salt thereof which exhibits an excellent HIV protease inhibitory activity and an excellent bioavailability from digestive tracts, and an anti-AIDS agent comprising said dipeptide compound as an effective ingredient. ##STR1## (wherein R.sub.1 represents 5-membered or 6-membered monocyclic hydrocarbon group or heterocyclic group wherein more than one carbon atom of said monocyclic hydrocarbon group is substituted with hetero atom. X represents methylene group (--CH.sub.2 --), chloromethylene group(--CH(Cl)--), oxygen atom sulfur atom or sulfonyl group (--SO.sub.2 --). R.sub.21 and R.sub.22 each represents hydrogen atom or aliphatic hydrocarbon group having 1-6 carbons. R.sub.3 represents aliphatic hydrocarbon group or monovalent group derived from aromatic monocyclic hydrocarbon having 1-6 carbons.Type: GrantFiled: August 21, 1998Date of Patent: October 5, 1999Assignee: Japan Energy CorporationInventors: Ryohei Kato, Tsutomu Mimoto, Tominaga Fukazawa, Naoko Morohashi, Yoshiaki Kiso
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Patent number: 5959098Abstract: The present invention provides novel processes for the large scale preparation of arrays of polymer sequences wherein each array includes a plurality of different, positionally distinct polymer sequences having known monomer sequences. The methods of the invention combine high throughput process steps with high resolution photolithographic techniques in the manufacture of polymer arrays.Type: GrantFiled: April 17, 1996Date of Patent: September 28, 1999Assignee: Affymetrix, Inc.Inventors: Martin Goldberg, Martin Diggelman, Earl Hubbell, Glenn McGall, Nam Quoc Ngo, Macdonald Morris, Mel Yamamoto, Jennifer Tan, Richard P. Rava
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Patent number: 5932550Abstract: The present invention provides a novel dipeptide compound or pharmaceutically acceptable salt thereof which exhibits an excellent HIV protease inhibitory activity and an excellent bioavailability from digestive tracts, and an anti-AIDS agent comprising said dipeptide compound as an effective ingredient.General formula (I): ##STR1## (wherein R.sub.1 represents 5-membered or 6-membered monocyclic hydrocarbon group or heterocyclic group wherein more than one carbon atom of said monocyclic hydrocarbon group is substituted with hetero atom. X represents methylene group (--CH.sub.2 --), chloromethylene group(--CH(Cl)--), oxygen atom sulfur atom or sulfonyl group (--SO.sub.2 --). R.sub.21 and R.sub.22 each represents hydrogen atom or aliphatic hydrocarbon group having 1-6 carbons. R.sub.3 represents aliphatic hydrocarbon group or monovalent group derived from aromatic monocyclic hydrocarbon having 1-6 carbons.Type: GrantFiled: June 26, 1996Date of Patent: August 3, 1999Assignee: Japan Energy CorporationInventors: Ryohei Kato, Tsutomu Mimoto, Tominaga Fukazawa, Naoko Morohashi, Yoshiaki Kiso
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Patent number: 5888963Abstract: A method for promoting bone growth in a patient (e.g., a mammal such as a human) said method including the step of administering a therapeutically effective amount of adrenomedullin or an adrenomedullin agonist to said patient.Type: GrantFiled: April 18, 1996Date of Patent: March 30, 1999Assignees: Auckland UniServices Limited, The Administrators of The Tulane Educational FundInventors: David H. Coy, Jillian Cornish, Ian Reginald Reid, Garth James Smith Cooper
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Patent number: 5854389Abstract: Process for the preparation of modified proteins comprising the coupling of a first peptide segment having a haloacyl group at the N-terminus thereof with a second peptide segment having a carbonylthiol group at the C-terminus thereof are disclosed. Novel modified proteins produced by the process are also disclosed.Type: GrantFiled: September 26, 1994Date of Patent: December 29, 1998Assignee: The Scripps Research InstituteInventors: Stephen B. H. Kent, Martina Schnolzer-Rackwitz
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Patent number: 5817752Abstract: This invention relates generally to cyclic polypeptides comprising a thioether linkage and methods for their preparation. More particularly, this invention relates to halogenated polypeptides having at least one haloalanine-like amino acid, and methods for their preparation which involve converting the hydroxyl group (i.e., --OH) of a serine-like amino acid to a halo group (i.e., --X where X is Cl, Br, or I) with the aid of a phosphorus-based halogenation reagent such as a triphenylphosphine dihalide (i.e., (C.sub.6 H.sub.5).sub.3 PX.sub.2, wherein X is Cl, Br, or I), a triphenylphosphite dihalide (i.e., (C.sub.6 H.sub.5 O).sub.3 PX.sub.2, wherein X is Cl, Br, or I), or a mixture of triphenylphosphine or triphenylphosphite with a halohydrocarbon (i.e., "halo-conversion").Type: GrantFiled: November 12, 1996Date of Patent: October 6, 1998Assignee: La Jolla Pharmaceutical CompanyInventor: Lin Yu
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Patent number: 5776718Abstract: The invention relates to novel reversible protease inhibitors. The inhibitors are specific to cysteine proteases.Type: GrantFiled: March 20, 1996Date of Patent: July 7, 1998Assignee: Arris Pharmaceutical CorporationInventors: James T. Palmer, David Rasnick, Jeffrey Lee Klaus
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Patent number: 5773617Abstract: The present invention relates to a reagent and to a process which are useful, when carrying out an organic synthesis, for cleaving an allylic group from a function which is protected with the latter.This reagent is defined in that it contains:a) a solvent system;b) a catalyst containing at least one element from column VIII of the Periodic Table of the Elements, the said element from column VIII of the Periodic Table being coordinated with at least one coordination agent which is soluble in the said solvent system;c) a compound which is at least partially soluble in the said solvent system and which contains at least one nucleophilic function.Application to organic synthesis.Type: GrantFiled: February 22, 1996Date of Patent: June 30, 1998Assignee: Rhone-Poulenc ChimieInventors: Jean-Marie Bernard, Errol Blart, Jean-Pierre Genet, Sandrine Lemaire-Audoire, Monique Savignac
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Patent number: 5750767Abstract: The present invention is directed to the process of preparing a peptide comprising reacting a first amino acid or peptide with an amino acid fluoride of the formula: ##STR1## or the acid fluoride salts thereof wherein BLK is an N-amino protecting groupAA is an amino acid residue andX is H or a protecting group useful,and the first amino and peptide have a free amino group and a blocked carboxy end.Type: GrantFiled: June 6, 1995Date of Patent: May 12, 1998Assignee: Research Corporation Technologies, Inc.Inventors: Louis A. Carpino, Ayman Ahmed El-Faham
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Patent number: 5733881Abstract: Compounds of the formula I as well as methods for their preparation, their pharmaceutical preparations and their use. ##STR1## The compounds of formula I are useful in therapy, especially as analgesics and as immunosuppresive agents.Type: GrantFiled: August 22, 1995Date of Patent: March 31, 1998Assignee: Astra ABInventor: Peter Schiller
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Patent number: 5726243Abstract: A triple-helical polypeptide of the formula: ##STR1## is provided wherein: Z is Hyp or Pro; each X and Y is an amino acid such that (Gly-X-Y).sub.m is a sequence of a collagen cell adhesion site; said X and Y may be the same or different and each (Gly-X-Y) may be the same or different; O is an amino acid having a single side-chain amino group; J is an amino acid capable of acting as a chromophore; U is an amino acid; u=0 or 1; n.ltoreq.30; m.ltoreq.30; m+n.ltoreq.30; and j.gtoreq.1. Methods of making these compounds and intermediates used in the methods, are also provided.Type: GrantFiled: July 3, 1996Date of Patent: March 10, 1998Assignee: Regents of the University of MinnesotaInventor: Gregg B. Fields
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Patent number: 5723598Abstract: The present invention describes an encoded combinatorial chemical library comprised of a plurality of bifunctional molecules having both a chemical polymer and an identifier oligonucleotide sequence that defines the structure of the chemical polymer. Also described are the bifunctional molecules of the library, and methods of using the library to identify chemical structures within the library that bind to biologically active molecules in preselected binding interactions.Type: GrantFiled: June 18, 1996Date of Patent: March 3, 1998Assignee: The Scripps Research InstituteInventors: Richard Lerner, Kim Janda, Sydney Brenner
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Patent number: 5712418Abstract: The present invention is directed to the process of preparing a peptide comprising reacting a first amino acid or peptide with an amino acid fluoride of the formula: ##STR1## or the acid fluoride salts thereof wherein BLK is an N-amino protecting groupAA is an amino acid residue andX is H or a protecting group useful,and the first amino and peptide have a free amino group and a blocked carboxy end.Type: GrantFiled: August 2, 1994Date of Patent: January 27, 1998Assignee: Research Corporation Technologies, Inc.Inventors: Louis A. Carpino, Ayman Ahmed El-Faham
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Patent number: 5700910Abstract: N-Acyl-S-(2-hydroxyalkyl)cysteines, their preparation and their use as intermediates for the preparation of synthetic immunoadjuvants and synthetic vaccines.Compounds of the formula I ##STR1## in which the substances X, Y, R, R.sup.1 and R.sup.2 have the meanings mentioned, are suitable for the preparation of lipopeptides and lipoamino acids.Type: GrantFiled: June 7, 1995Date of Patent: December 23, 1997Assignee: Hoechst AktiengesellschaftInventors: Jorg Metzger, Karl-Heinz Wiesmuller, Gunther Jung
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Patent number: 5648462Abstract: Disclosed is a method of purifying a mature peptide with a free N-terminus group from a mixture of peptides comprising the mature peptide and immature end-capped peptides. The peptides are bound to a solid-phase support and are produced by solid phase synthesis. The mixture is contacted with a linker comprising a functional group at each terminus. The functional group at one terminus has the structure --SO.sub.2 --CH.sub.2 --CH.sub.2 --X, wherein X is an activated carbonate group which reacts selectively with N-terminus of the mature peptide to form a urethane linkage. The functional group at the other terminus is a thiol protected with an acid labile group. After cleaving the peptides from the solid support and thiol protecting group with acid, the mature peptide is separated from the mixture by forming a covalent bond between the liberated thiol and a solid support. Treatment with base cleaves the mature peptide from the linker to give a purified mature peptide.Type: GrantFiled: January 27, 1995Date of Patent: July 15, 1997Assignee: Setsuko FunakoshiInventors: Susumu Funakoshi, Hiroyuki Fukuda
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Patent number: 5576419Abstract: A triple-helical polypeptide of the formula: ##STR1## is provided wherein: Z is Hyp or Pro; each X and Y is an amino acid such that (Gly-X-Y).sub.m is a sequence of a collagen cell adhesion site; said X and Y may be the same or different and each (Gly-X-Y) may be the same or different; O is an amino acid having a single side-chain amino group; J is an amino acid capable of acting as a chromophore; U is an amino acid; u=0 or 1; n.ltoreq.30; m.ltoreq.30; m+n.ltoreq.30; and j.gtoreq.1. Methods of making these compounds and intermediates used in the methods, are also provided.Type: GrantFiled: September 27, 1995Date of Patent: November 19, 1996Assignee: Regents of the University of MinnesotaInventor: Gregg B. Fields
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Patent number: 5541289Abstract: A method for incorporating novel phosphine containing amino acids into peptide sequences is provided. The resulting phosphine-containing peptides can be used to bind a transition metal between two phosphine moieties presented on an amino acid in a peptide. The resulting phosphine-containing peptide metal complex is useful as a stereoselective catalyst of a chemical reaction or as a means for delivering a metal selectively to a target tissue or organ for medical uses.Type: GrantFiled: March 30, 1994Date of Patent: July 30, 1996Assignee: Washington UniversityInventor: Scott R. Gilbertson
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Patent number: 5538897Abstract: A method for correlating a peptide fragment mass spectrum with amino acid sequences derived from a database is provided. A peptide is analyzed by a tandem mass spectrometer to yield a peptide fragment mass spectrum. A protein sequence database or a nucleotide sequence database is used to predict one or more fragment spectra for comparison with the experimentally-derived fragment spectrum. In one embodiment, sub-sequences of the sequences found on the database which define a peptide having a mass substantially equal to the mass of the peptide analyzed by the tandem mass spectrometer are identified as candidate sequences. For each candidate sequence, a plurality of fragments of the sequence are identified and the masses and m/z ratios of the fragments are predicted and used to form a predicted mass spectrum.Type: GrantFiled: March 14, 1994Date of Patent: July 23, 1996Assignee: University of WashingtonInventors: John R. Yates, III, James K. Eng