Of Amino Group Patents (Class 530/337)
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Patent number: 6750312Abstract: A method for preparing a solid support material for carrying out a chemical reaction, said method comprising the following steps: (i) reacting an amino functionalised solid material with a carboxylic acid having at least two similarly protected amino groups to form amide bonds between them, (ii) removing protecting groups in a single step, (iii) optionally repeating steps (i) and (ii) one or more times using the product of the preceding step as the amino functionalised solid material, and (iv) connecting a linkage agent to at least some of the free NH2 groups of the product. The method increases the loading capacity of the solid support material. It is particularly useful in connection with peptide synthesis.Type: GrantFiled: March 26, 2002Date of Patent: June 15, 2004Assignee: Avecia LimitedInventors: Craig Stephen Harris, Donald Alfred Wellings, Francis Joseph Montgomery, Richard John Brown
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Patent number: 6747125Abstract: Peptides which include unnatural amino acids and which either promote or inhibit the secretion of gonadotropins by the pituitary gland and inhibit the release of steroids by the gonads. Administration of an effective amount of such peptides that are GnRH antagonists prevents ovulation of female mammalian eggs and/or the release of steroids by the gonads and may be used to treat steroid-dependent tumors. The agonists can be used for control of reproduction processes, to treat precocious puberty, endometriosis, and the like. The peptides are analogs of the decapeptide GnRH wherein there is at least one residue of an unnatural amino acid in the 3-, 5-, 6- and/or 8-positions.Type: GrantFiled: October 7, 1996Date of Patent: June 8, 2004Assignee: The Salk Institute for Biological StudiesInventors: Carl A. Hoeger, Jean E. F. Rivier, Paula Guess Theobald, John S. Porter
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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: 6627609Abstract: The invention relates to peptides which contain N-methylated amino acid units and have improved water solubility. Medicaments in which the peptides according to the invention are contained can be used for the treatment of hormone-dependent tumours and hormone-influenced non-malignant disorders.Type: GrantFiled: March 14, 2000Date of Patent: September 30, 2003Assignee: Zentaris AGInventors: Michael Bernd, Bernhard Kutscher, Eckhard Günther, Peter Romeis, Thomas Reissmann, Thomas Beckers
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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: 6548644Abstract: Processes for conjugating proteins with polyethylene glycol are disclosed. The disclosed processes provide modified proteins having little or no decrease in their activity and include the steps of protecting one or more sites on the protein, contacting the protected protein with polyethylene glycol under conditions suitable for conjugating the polyethylene glycol to the protein, and deprotecting the protein. This advantageous retention of a desired protein activity is attributed to the availability of one or more protein binding sites which is unaltered in the conjugation process and thus remains sterically free to interact with a binding partner ligand or cognate subsequent to the conjugation process.Type: GrantFiled: March 10, 1997Date of Patent: April 15, 2003Assignee: Immunex CorporationInventor: Dean K. Pettit
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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: 6433135Abstract: PEG-LHRH analog conjugates, where a PEG moiety is covalently bound to a serine residue of a LHRH analog either directly or via a bifunctional linker molecule, such as an amino acid, and methods for producing these conjugates are provided in the present invention. Also provided are a pharmaceutical composition and a method for treating pathologies in which LHRH analog administration is beneficial.Type: GrantFiled: October 30, 2000Date of Patent: August 13, 2002Assignee: Applied Research Systems ARS Holding N.V.Inventors: Nabil El-Tayar, Xuan Zhao, Michael D. Bentley
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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: 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: 6372717Abstract: The invention concerns the use of peptides of general formula R1-L-Tyr-L-Arg-R2 in which R1=H or a R3-C=0 with R3=a C1 to C20 alkyl chain, linear or branched, saturated or unsaturate, hydroxylated or not, or with R3=an aryl, aryl-alkyl or alkyloxy or aryloxy or arylalkyloxy group, and in which R2=OH or a O-R4 group with R4=a C1 to C20 alkyl chain, or R2=a NH2, NHX or NXX group with X=a C1 to C4 alkyl chain. The peptides have a soothing effect on the skin, including by topical application, and attenuates the effects of benign skin sores (after shave irritation, sunstroke, frostbite, chaps, depilation). They are used in acceptable cosmetic excipients and in effective in vivo concentrations.Type: GrantFiled: February 23, 1999Date of Patent: April 16, 2002Assignee: Sederma S.A.Inventor: Daniel Greff
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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: 6251625Abstract: The invention concerns a process for the enzymatic preparation of protected di- and oligopeptides and the separation of the protective groups used. The process according to the invention enables peptides to be synthesized simply and economically and the protective group to be separated carefully. The process comprises three reaction steps: 1. Preparation of N-carbamoyl amino acid or N-carbamoyl amino acid derivatives; 2. Formation of the peptide bond between the carbamoyl-protected electrophile and nucelophile; and 3. Separation of the carbamoyl-protective group.Type: GrantFiled: April 3, 1998Date of Patent: June 26, 2001Assignee: Degussa AktiengesellschaftInventors: Andreas Bommarius, Karlheinz Drauz, Uwe Eichhorn, Hans-Dieter Jakubke, Matthias Kottenhahn
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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: 6075141Abstract: This invention provides Ddz-amino acid pentafluorophenyl esters and Ddz-amino acid 3,4-dihydro-3-hydroxy-4-oxo-1,2,3-benzotriazine (ODhbt) esters and their side-chain protected derivatives. Preferred esters and derivatives are crystalline solids. The invention also provides (.alpha.,.alpha.-Dimethyl-3,5-dimethoxybenzyl)-p-methoxycarbonylphenylcarb onate, an improved reagent for the introduction of the Ddz group. Pfp and ODhbt esters of this invention have favorable coupling to racemization ratios and are particularly suited for automated solid-phase peptide synthesis. The invention relates in addition to methods of making the esters of this invention and to methods of using these esters in peptide synthesis.Type: GrantFiled: July 10, 1997Date of Patent: June 13, 2000Assignee: University of Georgia Research Foundation, Inc.Inventor: Robert I. Carey
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Patent number: 6060586Abstract: Ureins are obtained by reaction, in basic medium, between an N.sup..omega. -(aryloxycarbonyl)diamino acid and a compound containing a free amino group. The chirality of the compounds is outstandingly well preserved.Type: GrantFiled: June 17, 1997Date of Patent: May 9, 2000Assignee: Solvay (Societe Anonyme)Inventors: Roland Callens, Georges Blondeel, Marc Anteunis, Frank Becu
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Patent number: 6028172Abstract: A solid phase peptide synthesis reactor system and method of operating the reactor are provided. The reactor system includes a basket rotatable about an axis within a housing and a receiver which delivers fluid to, and collects fluid from, the housing. The basket has a perforate side wall against which a resin cake for the peptide synthesis is formed. The reactor and receiver form a loop or circuit through which solutions are circulated. The circulation of the solutions prevents the reactor from flooding so that the basket will not be submerged in solution and allows for the use of less liquid. Thus greater amino acid concentrations may be used. The method includes forming a resin cake of uniform depth on the wall of the spinning basket and spraying the solutions against the resin cake while spinning the basket. The solutions will pass through the resin cake and drain to the receiver to be circulated or recycled through the system or discharged from the system.Type: GrantFiled: March 9, 1999Date of Patent: February 22, 2000Assignee: Mallinckrodt Inc.Inventors: Nicholas Stepaniuk, Keith Tomazi, Michael C. Stapleton
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Patent number: 5994588Abstract: Disclosed are novel compounds which are used as linkers to bind peptides to solid support. The novel compounds can be used for the purification of synthesized peptides and are represented by the following structural formula:X--NH--(CH.sub.2).sub.n --SO.sub.2 --CH.sub.2 --CH.sub.2 --O--CO--Y;n is an integer from 1-4; X is a thiol functionalized with a protecting group that is cleavable under acidic conditions; and Y is a leaving group.Type: GrantFiled: June 2, 1995Date of Patent: November 30, 1999Assignee: Setsuko FunakoshiInventors: Susumu Funakoshi, Hiroyuki Fukuda
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Patent number: 5965770Abstract: Compounds having the general formula: ##STR1## in which R3 represents an aryl group which is unsubstituted or substituted by one or more alkyl groups containing 1 to 4 carbon atoms; R4 represents a hydrogen atom, a group for protecting the amino functional group, an amino acid or a peptide some of whose functional groups are optionally substituted by a protecting group or by an activating group; R5 represents a hydroxy group, a halogen atom, a group for protecting the carboxyl functional group, an activating group, an amino group, an amino acid or a peptide some of whose functional groups are optionally substituted by a protecting group or by an activating group; and n is an integer from 1 to 10.Type: GrantFiled: October 31, 1997Date of Patent: October 12, 1999Assignee: SolvayInventors: Marc Anteunis, Frank Becu, Roland Callens, Georges Blondeel
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Patent number: 5965699Abstract: A label-based assay is described, through modifications of substrate strure and derivatization of serum albumin, which can be used to determine type A proteolytic activity without separation of products.Type: GrantFiled: November 6, 1996Date of Patent: October 12, 1999Assignee: The United States of America as represented by the Secretary of the ArmyInventors: James J. Schmidt, Karen A. Bostian
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Patent number: 5962502Abstract: Derivatives of glutamic and aspartic of formula (I) are described ##STR1## where the compounds are potent receptor antagonists of gastrin at the peripheral level and of cholecystokinin at the level of the central nervous system.Type: GrantFiled: April 8, 1996Date of Patent: October 5, 1999Assignee: Rotta Research Laboratorium S.p.A.Inventors: Francesco Makovec, Walter Peris, Lucio C. Rovati, Luigi A. Rovati
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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: 5955434Abstract: The invention relates to N-terminal Fmoc-protected peptide combinations that form gels in water and diverse organic solvents, and whose representative overall formulas are: (I), where R.sup.1 is CH.sub.3, CH.sub.2 --CH(CH.sub.3).sub.3, CH(CH.sub.3)CH.sub.2 CH.sub.3, R.sup.2 is H, CH.sub.3, CH.sub.2 OH, (CH.sub.2).sub.n --COOH, (CH.sub.2)4--NH--CO--OCH.sub.2 C.sub.6 H.sub.5, R.sup.3 is dipeptide remainder, m is 0 or 1 and, n is 1 or 2; or (II), where R1 is CH.sub.3, CH.sub.2 --CH(CH.sub.3)2, or CH(CH.sub.3)CH.sub.2 CH3, R2 is CH2--CH(CH3)2, R3 is H, CH.sub.3, CH.sub.2 OH, (CH.sub.2).sub.n --COOH, or (CH.sub.2)4--NH--CO--OCH.sub.2 C.sub.6 H.sub.5, R.sub.4 is tripeptide remainder, m is 0 or 1 and, n is 1 or 2. These types of peptides form gels in aqueous solutions and are biologically compatible and may be useful for drug delivery, antigen delivery and may be useful as food additives to retard spoilage and act as fillers.Type: GrantFiled: August 9, 1996Date of Patent: September 21, 1999Assignee: Brigham & Women's HospitalInventors: Paul A. Janmey, Rolands Vegners
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Patent number: 5942601Abstract: Methods and compositions are provided for synthesizing peptides with sulfonyl protecting groups. In the subject methods, an sulfonyl group .alpha.-amino protected amino acid is contacted with a second amino acid monomeric unit under coupling conditions so that the protected amino acid and second amino acid monomeric unit are joined by a peptide bond. The contacting step may be repeated one more additional times to obtain a peptide of desired length. Also provided are methods of site specific modification using the subject sulfonyl protecting groups. The subject methods find particular use in methods of solid phase peptide synthesis.Type: GrantFiled: November 21, 1997Date of Patent: August 24, 1999Assignee: The Reagents of The University of CaliforniaInventors: Stephen C. Miller, Thomas S. Scanlan
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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: 5859191Abstract: A peptide comprising a free terminal alpha amine is treated with an aryl sulfonamide activating agent, resulting in an activated amide. The resulting activated amide is deprotonated with a base and modified by the addition of a substituent group. The aryl sulfonamide activating group is cleaved using a nucleophilic substitution reaction. The method is particularly useful for the modification of peptides at specific N-alpha positions, and is compatible with conventional solid phase peptide synthesis, including those that utilize Fmoc protecting groups.Type: GrantFiled: December 5, 1996Date of Patent: January 12, 1999Assignee: The Regents of the University of CaliforniaInventors: Stephen Miller, Thomas S. Scanlan
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Patent number: 5840682Abstract: The invention is directed to a compound of formula ##STR1## in which R represents a hydroxyl, alkyloxy, phenylalkyloxy or --NH--CH.sub.2 --COOH radical, R.sub.1 represents a hydrogen atom, an adamantylacetyl, adamantylcarbonyl, norbornylacetyl, norbornylphenoxycarbonyl, benzoyl, nicotinoyl, 4-phenylbenzoyl, 4-tert-butylbenzoyl or 2-pyrrolidinecarbonyl radical or a protective group for an amine functional group, R.sub.2 represents an Arg or Lys residue, R.sub.3 represents an Arg or Lys residue, R.sub.4 represents a Pro residue, m, n and p, which are the identical or different, represent a number equal to 0 or 1, R.sub.5 and R.sub.6 are identical and represent a hydroxyl or methoxy radical and R.sub.7 represents a hydrogen, chlorine, bromine or iodine atom or a nitro radical, or the compound wherein one or a number of peptide bonds between two amino acid residues are replaced by --CH.sub.2 --NH bonds or the peptide bond between the R.sub.2 and R.sub.3 amino acid residues is replaced by a CH.dbd.Type: GrantFiled: November 19, 1996Date of Patent: November 24, 1998Assignee: Rhone-Poulenc Rorer S.A.Inventors: Francois-Frederic Clerc, Marie-Christine Dubroeucq, Gerard Helynck, Jean Leboul, Jean-Paul Martin
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Patent number: 5840841Abstract: Method and apparatus for synthesizing biopolymers, such as polypeptides and polynucleotides. The apparatus includes plural reaction vessels in which subunit coupling to biopolymers in a particle suspension is carried out. The vessels are connected to common valving structure for use in mixing the suspension and removing suspension liquid. In one embodiment, a robotic arm in the apparatus is operable to transfer reaction solution to the reaction vessels, and to transfer particle suspensions from the reaction vessels to a mixing vessel and back to the reaction vessels. The method can be used to produce preferably equi-molar amounts of different-sequence biopolymers, such as polypeptides and polynucleotides.Type: GrantFiled: May 8, 1997Date of Patent: November 24, 1998Assignee: Chiron CorporationInventors: Ronald N. Zuckermann, Verena D. Heubner, Daniel V. Santi, Michael A. Siani
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Patent number: 5777077Abstract: A method for removing an allyl protecting group from an allyl-protected derivative of a biologically relevant amino acid is disclosed. One relevant aspect of the method is the use of soluble organometallic catalyst, such as an organopalladium catalyst. Preferably, soluble tetrakistriphenylphosphine palladium (0) is used. The allyl deprotection method now disclosed is suitable for use on an instrument for automated peptide synthesis. Methods of preparing the soluble organometallic catalyst are also disclosed, as are soluble catalyst compositions.Type: GrantFiled: February 20, 1997Date of Patent: July 7, 1998Assignee: PerSeptive Biosystems, Inc.Inventors: Fernando Albericio, Steven A. Kates
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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: 5770692Abstract: Method of synthesising peptides containing one or more amino acid residues bearing an N-carbamoyl functional group, by aminolysis of N-aryloxycarbonyl derivatives, which are excellent synthesis intermediates for the preparation of various peptides containing amino acid residues bearing a ureino group, such as citrulline, homocitrulline, 2-amino-4-ureidobutyric residues.Type: GrantFiled: June 22, 1994Date of Patent: June 23, 1998Inventors: Marc Anteunis, Frank Becu, Roland Callens, Georges Blondeel
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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: 5734011Abstract: Compositions and methods of incorporating ligand precursors and ligands at any location within a peptide during peptide synthesis are disclosed. Derivatives of 2,4,5-triaminopentanoic acid and .gamma.-aminoglutamic acid are selectively incorporated into the peptide during solid phase or liquid phase synthesis, depending upon the choice of protecting groups. Ligand synthesis may then be completed at a later time to produce N.sub.3 S, N.sub.2 S.sub.2, and EDTA type chelating agents.Type: GrantFiled: June 6, 1995Date of Patent: March 31, 1998Assignee: Mallinckrodt Medical, Inc.Inventors: T. Jeffrey Dunn, Ananthachari Srinivasan
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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: 5714580Abstract: Novel compounds having activity against trypsin are disclosed. Specifically, novel peptide aldehyde analogues that have substantial potency and specificity as inhibitors of mammalian pancreatic trypsin are presented. The compounds are useful in the prevention and treatment of the tissue damage or destruction associated with pancreatitis.Type: GrantFiled: May 31, 1995Date of Patent: February 3, 1998Assignee: Corvas International, Inc.Inventors: Terence K. Brunck, Michael G. Pepe, Daniel A. Pearson, Thomas R. Webb
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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: 5705610Abstract: Method and apparatus for synthesizing biopolymers, such as polypeptides and polynucleotides. The apparatus includes plural reaction vessels in which subunit coupling to biopolymers in a particle suspension is carried out. The vessels are connected to common valving structure for use in mixing the suspension and removing suspension liquid. In one embodiment, a robotic arm in the apparatus is operable to transfer reaction solution to the reaction vessels, and to transfer particle suspensions from the reaction vessels to a mixing vessel and back to the reaction vessels. The method can be used to produce preferably equi-molar amounts of different-sequence biopolymers, such as polypeptides and polynucleotides.Type: GrantFiled: October 1, 1993Date of Patent: January 6, 1998Assignee: Chiron CorporationInventors: Ronald N. Zuckermann, Verena D. Heubner, Daniel V. Santi, Michael A. Siani
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Patent number: 5698676Abstract: A process of synthesizing a peptide using an alkylene oxide as an acid scavenger is provided. A process of the present invention can be used in a solid phase or solution phase synthetic process where peptide synthesis occurs by the sequential addition of N-.alpha.-amino-Boc-protected residues followed by acid deprotection of that N-.alpha.-amino protecting group and scavenging of the acid.Type: GrantFiled: November 30, 1995Date of Patent: December 16, 1997Assignee: Abbott LaboratoriesInventor: Madhup K. Dhaon
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Patent number: 5684132Abstract: The present invention relates to a process for preparing protected amines or amino acids. The invention furthermore relates to the use of tocopheryl radicals or radicals derived therefrom as protective groups for amines and amino acids, and to compounds obtained in this process as intermediates and to processes for preparing dipeptides and oligopeptides.Type: GrantFiled: December 4, 1995Date of Patent: November 4, 1997Assignee: BASF AktiengsellschaftInventors: Thomas Rosenau, Wolf-Dieter Habicher, Chen-Loung Chen
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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: 5644028Abstract: A process for producing peptide derivatives of formula (1) or salts thereof: ##STR1## which comprises condensation of peptide derivative of formula (2): ##STR2## with carboxylic acid of formula (3): ##STR3## or condensation of a peptide derivative of formula (4): ##STR4## with a protected amino acid of formula (5'): ##STR5## wherein R.sup.1 and R.sup.2 are a lower alkyl group or hydrogen atom, R.sup.3 is a lower alkyl group, X is a methylthiomethyl, methanesulfonylmethyl, carbamoylmethyl, or a lower alkyl group, Ar is an aryl or heteroaryl group, and A.sup.4 is Ar--O--CH.sub.2 --CO. The peptide derivatives and salts thereof are useful as the human immunodeficiency virus (HIV) protease inhibitors.Type: GrantFiled: December 28, 1994Date of Patent: July 1, 1997Assignee: Japan Energy CorporationInventors: Tsutomu Mimoto, Sumitsugu Kisanuki, Osamu Takahashi, Yoshiaki Kiso
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Patent number: 5639859Abstract: Carboxylate protective groups, a process for their preparation, their coupling to a funcitonal group, and their useCarboxylates of polar, hydrophilic alcohols of the formula ##STR1## in which R is an unbranched or branched organic radical which contains, as polar members between aliphatic or araliphatic hydrocarbon bridges, ether oxygens, amine nitrogen groups or a mixture of ether and amine groups which can be incorporated into a cyclic structure, where the total length does not exceed 20 members and where, in the case of polyethylene glycol [(CH.sub.2 --CH.sub.2 --O).sub.n ], n indicates the number of the members and is defined as any integer, andR' is an aliphatic or araliphatic radical which has at least one functional group,are suitable as protective groups since they can be introduced selectively into functional groups of organic compounds and eliminated specifically by lipases.Type: GrantFiled: May 15, 1995Date of Patent: June 17, 1997Assignee: Hoechst AktiengesellschaftInventors: Horst Kunz, Gunther Braum, Peter Braun