Protecting Or Removing Protective Groups, E.g., Carboxyl Group Protection, Etc. Patents (Class 530/335)
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Patent number: 6413785Abstract: The subject invention involves processes for making 1-aminohydantoin compounds using a solid support resin, comprising the following steps; (a) preparing a resin-bound protected &agr;-hydrazinyl ester; (1) by reacting the resin with an &agr;-bromo carboxylic acid, then with a protected hydrazine; or (2) by reacting the resin with a protected &agr;-hydrazinyl carboxylic acid; (b) preparing a resin-bound imine by removing the blocking group from the hydrazinyl moiety, then reacting the unprotected hydrazinyl moiety with an aldehyde or ketone; (c) preparing a resin-bound secondary urea: (1) by reacting the imine with p-nitrophenylchloroformate or trisphosgene, then with a primary amine; or (2) by reacting the imine with an isocyanate, and (d) preparing the 1-aminohydantoin compound by removing the secondary urea from the resin and cyclizing it.Type: GrantFiled: August 18, 2000Date of Patent: July 2, 2002Assignee: The Procter & Gamble Co.Inventors: Lawrence Joseph Wilson, David Edward Portlock, Min Li
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Patent number: 6410342Abstract: A method for photoeluting photocleavable linker-attached chemical compounds, and an apparatus suitable for implementing the method, are disclosed. According to the method, photocleavable linker-attached library compounds are photoeluted from solid support media under conditions of controlled light exposure and controlled temperature. An apparatus suitable for carrying out the present photoelution method includes means for substantially evenly illuminating the photocleavable linker, means for controlling illumination time and intensity, and means for controlling sample temperature.Type: GrantFiled: August 19, 1997Date of Patent: June 25, 2002Assignee: Pharmacopeia, Inc.Inventors: Rhett L. Affleck, Doug Hobbs, Ilya Feygin, Gregory L. Kirk, James A. Connelly, Ning Zhao, James P. Mueller, Peter Kieselbach
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Patent number: 6406844Abstract: A method and apparatus for preparation of a substrate containing a plurality of sequences. Photoremovable groups are attached to a surface of a substrate. Selected regions of the substrate are exposed to light so as to activate the selected areas. A monomer, also containing a photoremovable group, is provided to the substrate to bind at the selected areas. The process is repeated using a variety of monomers such as amino acids until sequences of a desired length are obtained. Detection methods and apparatus are also disclosed.Type: GrantFiled: June 1, 1995Date of Patent: June 18, 2002Assignee: Affymetrix, Inc.Inventors: Michael C. Pirrung, J. Leighton Read, Stephen P. A. Fodor, Lubert Stryer
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Publication number: 20020058788Abstract: The present invention provides a method for deprotecting a Fmoc protected amino group, said method comprising treating in a suitable medium the protected amino group with a base in the presence of a thiol compound to yield a deprotected amino group.Type: ApplicationFiled: August 24, 2001Publication date: May 16, 2002Inventor: James E. Sheppeck
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Patent number: 6383812Abstract: The present invention provides a novel method of synthesizing branched galactose-terminal glycoproteins. A number of these glycoproteins have binding affinity to the asialoglycoprotein receptor. The present invention also provides novel conjugates having branched galactose-terminal glycoproteins that is complexed to a therapeutically effective agent, such as an isolated protein, polysacharides, lipids and radioactive isotope. These conjugates may be used to deliver the therapeutically effective agent to mammalian cells generally, and to hepatocytes specifically.Type: GrantFiled: January 25, 2000Date of Patent: May 7, 2002Assignee: Academia SinicaInventors: Shui-Tein Chen, Weir-Torn Jiaang, Ping-Hui Tseng, Chun-Ming Huang
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Patent number: 6379679Abstract: Multiple branch peptide constructions formed from peptides derived from the envelope transmembrane glycoprotein gp41 of HIV, and including the consensus sequence RQGY preceded by 0 to 4 amino acid residues and succeeded by 2 to 4 amino acid residues, most preferably RQGYSPL, show increased receptor affinity and prevent cell-to-cell fusion. They have a direct virostatic effect. Because they present the same peptide sequence several times, these MBPCs are able to neutralize in vitro the different steps of virus envelope/cell membrane fusion, and infected cell membrane/uninfected cell membrane fusion of several strains of HIV-1 and HIV-2. These results open a potential use in treatment of HIV infection.Type: GrantFiled: June 29, 1999Date of Patent: April 30, 2002Assignee: Gellpep S.A.Inventors: Kamel Mabrouk, Jean-Marc Sabatier, Herve Rochat, Jurphaas Van Rietschoten
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Patent number: 6380156Abstract: Disclosed is a synthetic method for the preparation of analogs of Didemnin A (1), particularly the Amino-Hip analog of Didemnin A, also known as “AipDidemnin A” (8).Type: GrantFiled: June 28, 1999Date of Patent: April 30, 2002Assignee: The Board of Trustees of the University of IllnoisInventors: Kenneth L. Rinehart, Alexandra J. Katauskas
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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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Publication number: 20020048750Abstract: A method for the preparation of a chemical library, which method comprises synthesizing the library on a plurality of individually coded synthesis particles and wherein the particles are tracked during library synthesis under the control of robotic apparatus.Type: ApplicationFiled: December 27, 1999Publication date: April 25, 2002Inventors: ANTHONY ROBERT CORLESS, DAVID ANDREW WENN, RICHARD EDEN SHUTE
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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: 6372885Abstract: Method for preparing a combinatorial chemistry library of compounds of the formula R1—C(═O)—NH—R2, wherein R1 and R2 are as defined in the specification, which comprises acylating a combinatorial chemistry intermediate of the formula 1A wherein Y1, Y2, X, n, R1 and R2 are as defined in the specification to produce a compound of the formula wherein Y1, R1, R2 and X are as defined in the specification, followed by acidolytic cleavage of the resin bound linker to release the compound of the formula R1—C(═O)—NH—R2.Type: GrantFiled: May 20, 1999Date of Patent: April 16, 2002Assignee: Peptide Therapeutics LimitedInventors: Tony Johnson, Martin Quibell
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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: 6359113Abstract: The protective group having the following formula (I): Ar—L— (I) wherein Ar represents a substantially planar, fused ring system containing at least 4 aromatic rings, and L represents a group containing at least one carbon atom which is capable of bonding to a group to be protected.Type: GrantFiled: September 30, 1998Date of Patent: March 19, 2002Assignee: Rhodia ChimieInventors: Robert Ramage, Gilles Raphy
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Patent number: 6355490Abstract: The present invention relates to a process of coding and identifying individual members of a chemical combinatorial library synthesized on a plurality of solid supports which undergo mix and split synthesis. The process provides for tagging the solid supports with a coding identifier that is attached to the solid support and which can be decoded by infrared or raman spectroscopy when directly attached to the support.Type: GrantFiled: September 4, 1997Date of Patent: March 12, 2002Inventors: Jill Edie Hochlowski, Thomas J. Sowin, Daniel W. Norbeck, Anne-Laure Marie Grillot, Rolf E. Swenson
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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: 6346604Abstract: Cyclic pentapeptides having a &ggr;-turn and a &bgr;-turn wherein the cyclic pentapeptide has the following formula (I): Cyclo(—A1—A2—A3—A4—A5—) (I) wherein A1, A2, A3, A4 and A5 are amino acid residues; said pentapeptide having amino acid residues in positions 1-2-3 to form a &ggr;-turn, and amino acid residues in positions 3-4-5-1 to form a &bgr;-turn in combination with the &ggr;-turn; in which D-&agr;-amino acid residues are selected for A1, A3 and A5 and L-&agr;-amino acid residues are selected for A2 and A4 or wherein L-&agr;-amino acid residues are selected for A1, A3 and A5 and D-&agr;-amino acid residues are selected for A2 and A4; are provided.Type: GrantFiled: November 12, 1997Date of Patent: February 12, 2002Assignee: Takeda Chemical Industries, Inc.Inventors: Mitsuhiro Wakimasu, Hiroshi Inooka, Satoshi Endo, Takashi Kikuchi
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Patent number: 6331273Abstract: Combinations, called matrices with memories, of matrix materials with remotely addressable or remotely programmable recording devices that contain at least one data storage unit are provided. The matrix materials are those that are used in as supports in solid phase chemical and biochemical syntheses, immunoassays and hybridization reactions. The data storage units are preferably non-volatile antifuse memories. By virtue of this combination, molecules and biological particles, such as phage and viral particles and cells, that are in proximity or in physical contact with the matrix combination can be labeled by programming the memory with identifying information and can be identified by retrieving the stored information. Combinations of matrix materials, memories, and linked molecules and biological materials are also provided.Type: GrantFiled: June 7, 1995Date of Patent: December 18, 2001Assignee: Discovery Partners InternationalInventors: Michael P. Nova, Andrew E. Senyei, Gary S. David
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Patent number: 6323179Abstract: Specially designed non-mammalian GnRH analog decapeptides resistant to degradation by the placental enzyme, C-ase-1, or a post-proline peptidase, are disclosed. The GnRH analogs are further defined as analogs of Chicken II GnRH or Salmon GnRH. These non-mammalian analogs incorporate D-arginine, D-leucine, D-tBu-Serine or D-Trp at position 6 and ethylamide or aza-Gly-amide at position 10. The D-Arg (6)-Chicken II GnRH-ethylamide, D-Arg (6)-Chicken II GnRH-aza-Gly (10)-amide, the D-Arg (6)-Salmon GnRH ethylamide, and D-Arg (6)-Salmon GnRH-aza-Gly (10)-amide analogs are also provided, and demonstrate preferential binding to chorionic GnRH receptor that is greater relative to the biding of these analogs to pituitary GnRH receptor. These non-mammalian GnRH analogs may be used in pharmaceutical preparation, and specifically in various treatment methods as a contraceptive or post-coital contraceptive agent.Type: GrantFiled: October 15, 1999Date of Patent: November 27, 2001Inventor: Theresa Siler-Khodr
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Patent number: 6300470Abstract: The present invention provides substantially purified cryptdin peptides having a consensus amino acid sequence: X1-C-X2-C-R-X3-C-X4-E-X5-C-X6-C-C-X7 wherein X1 is 3 to 9 amino acids; X2 is one amino acid, preferably Y, H or R; X3 is 2 or 3 amino acids; X4 is three amino acids; X5 is five amino acids; X6 is 6 to 10 amino acids; and X7 is 0 to 9 amino acids.Type: GrantFiled: September 15, 1999Date of Patent: October 9, 2001Assignee: The Regents of the University of CaliforniaInventors: Michael E. Selsted, Andre J. Ouellette
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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: 6277957Abstract: A method is provided which facilitates and enables the production of a wide range of complex conjugates composed of similar or dissimilar units linked together by amide bonds. Said method for the production of acylthio derivatives, R′—CO—SA, involves reaction of a carboxylate, R′—CO—O− (or carboxylic acid R′—CO—OH) with an iso-thiouronium derivative (bearing SA) in the presence of base. Nucleophilic counterion forms of the iso-thiouronium salts confer significant rate enhancement. The processes are simple, generally applicable, efficient, and do not require the employment of noxious reagents. The production of complex protein-like products by the intermediary of acylthio esters generated by the process of this invention, provides a method which is compatible with mild methods of chain assembly; and is preferably applied when the second component in the ligation bears an amino terminal cysteine residue.Type: GrantFiled: March 23, 2000Date of Patent: August 21, 2001Inventors: Derek Hudson, Stewart Thompson
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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: 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: 6207644Abstract: The invention concerns pharmaceutically useful peptide derivatives of the formula (I), P—R1—R2—R3—R4, in which P, R1, R2, R3, and R4 have the various meanings defined herein, and their pharmaceutically acceptable salts, and pharmaceutical compositions containing them. The novel peptide derivatives are of value in treating MHC class II dependent T-cell mediated autoimmune or inflammatory diseases, such as rheumatoid arthritis. The invention further concerns processes for the manufacture of the novel peptide derivatives and the use of the compounds in medical treatment.Type: GrantFiled: April 16, 1999Date of Patent: March 27, 2001Assignee: Zeneca LimitedInventors: Richard William Arthur Luke, Ronald Cotton
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Patent number: 6194544Abstract: Cyclic penta- and hexa-peptide libraries containing one or more known amino acids, one or more randomized amino acids and a conformationally constraining element are disclosed. These peptide libraries may be used for screening for new bioactive peptides and for elucidating structural information pertinent to drug design.Type: GrantFiled: January 5, 1996Date of Patent: February 27, 2001Assignee: SmithKline Beecham CorporationInventors: William Francis Huffman, Michael Lee Moore
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Patent number: 6159706Abstract: The present invention provides a method for targeting toxic antimetabolites to gram negative infections. It provides a means of taking advantage of a key disease resistance mechanism to activate these drugs locally, and to overcome the resistance phenotype of the microbes. The invention further provides a method for selecting for antibiotic sensitivity, since a likely mechanism by which organisms are likely to gain resistance to the prodrugs is via loss of enzyme activity, which will make the bacteria sensitive to antibiotics once again.Type: GrantFiled: December 18, 1998Date of Patent: December 12, 2000Assignee: NewBiotics, Inc.Inventor: H. Michael Shepard
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Patent number: 6153743Abstract: Systems and methods of synthesizing probes on a substrate are provided. One or more shift reticles are utilized to uniformly add monomers to the substrate at specified locations. The shift reticles are shifted relative to the substrate between monomer addition steps. Additionally, characteristics of the desired probes may be specified at synthesis time.Type: GrantFiled: April 13, 1998Date of Patent: November 28, 2000Assignee: Affymetrix, Inc.Inventors: Earl A. Hubbell, Lubert Stryer
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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: 6127515Abstract: This invention is directed to a functionalized amino resin of formula ##STR1## wherein S is a solid support; R is H or alkyl; A is ##STR2## Y is OH or OCOR.sup.1 ; and R.sup.1 is aliphatic or aromatic which is useful for the solid phase synthesis of amides, peptides and hydroxamic acids.Type: GrantFiled: May 21, 1999Date of Patent: October 3, 2000Assignee: Aventis Pharmaceuticals Products Inc.Inventors: Franco Manfre, Benoit J. Vanasse, Richard F. Labaudiniere, George C. Morton
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Patent number: 6093799Abstract: A substrate for solid phase synthesis of the formula: ##STR1## is disclosed. Also disclosed are processes for preparing the substrate and intermediates useful therein. Among the novel intermediates are compounds of the formula: ##STR2## wherein t is 0 or 1; n is 3-20; R is OH, an activated ester or the residue of a solid support having a plurality of amino functionalities; A is --O-- or --NH-- and Q is hydrogen or a protecting group for an amine or alcohol.Type: GrantFiled: October 20, 1999Date of Patent: July 25, 2000Assignee: Pharmacopeia, Inc.Inventors: Ge Li, Sian Louise Griffiths, Edward McDonald, Libo Xu
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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: 6057425Abstract: The present invention provides a method of preparing substantially purified cryptdin peptides having a consensus amino acid sequence:X.sub.1 -C-X.sub.2 -C-R-X.sub.3 -C-X.sub.4 -E-X.sub.5 -C-X.sub.6 -C-C-X.sub.7wherein X.sub.1 is 3 to 9 amino acids; X.sub.2 is one amino acid, preferably Y, H or R; X.sub.3 is 2 or 3 amino acids; X.sub.4 is three amino acids; X.sub.5 is five amino acids; X.sub.6 is 6 to 10 amino acids; and X.sub.7 is 0 to 9 amino acids. The invention also provides a method of preparing substantially purified mouse cryptdin having a consensus amino acid sequence:X.sub.1 -L-X.sub.2 -C-Y-C-R-X.sub.3 -C-K-X.sub.4 -E-X.sub.5 -G-T-C-X.sub.6 -C-C-X.sub.7wherein X.sub.1 is 3 or 4 amino acids, preferably LRD, LSKK (SEQ ID NO: 1) or LRG; X.sub.2 is 1 amino acid, preferably V, L or I; X.sub.3 is 3 amino acids, preferably KGH or *RG, where * is S, T, K, I or A; X.sub.4 is 2 amino acids, preferably GR, RR or RG; X.sub.5 is 3 amino acids, preferably RMN, RVR, RVF HMN or HIN; X.sub.Type: GrantFiled: January 30, 1998Date of Patent: May 2, 2000Assignee: The Regents of the University of CaliforniaInventors: Michael E. Selsted, Andre J. Ouellette
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Patent number: 6048529Abstract: The invention relates to a procedure for synthesis of well-defined conjugates of peptides to the tolerogenic polymer monomethoxypolyethylene glycol (mPEG) or polyvinyl alcohol (PVA). This method results in the preparation of conjugates in which one molecule of tolerogenic polymer is specifically coupled to one or the other or both of the termini of an otherwise unaltered peptide molecule. A synthetic peptide synthesized using this method and corresponding to a myasthenogenic region of an acetylcholine receptor was conjugated to monomethoxypolyethylene glycol. Injection of animals with the mPEG-conjugate and subsequent immunization with whole receptor suppressed the development of experimental autoimmune myasthenia gravis (EAMG) by electrophysiological criteria. Specifically-conjugated, tolerogenic peptides are also disclosed for diseases as diverse as ragweed pollen allergy and Grave's disease.Type: GrantFiled: March 29, 1995Date of Patent: April 11, 2000Inventors: M. Zouhair Atassi, Tetsuo Ashizawa
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Patent number: 6046306Abstract: PNA synthesis using an amino protective group which is labile to weak acids.Type: GrantFiled: September 11, 1997Date of Patent: April 4, 2000Assignee: Hoechst AktiengesellschaftInventors: Gerhard Breipohl, Eugen Uhlmann
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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: 6015881Abstract: The present invention relates, first, to methods for the synthesis of peptides, in particular T-20 (also referred to as "DP-178"; SEQ ID NO:1) and T-20-like peptides. Such methods utilize solid and liquid phase synthesis procedures to synthesize and combine groups of specific peptide fragments to yield the peptide of interest. The present invention further relates to individual peptide fragments which act as intermediates in the synthesis of the peptides of interest (e.g., T-20). The present invention still further relates to groups of such peptide intermediate fragments which can be utilized together to produce full length T-20 and T-20-like peptides.Type: GrantFiled: May 1, 1998Date of Patent: January 18, 2000Assignee: Trimeris, Inc.Inventors: Myung-Chol Kang, Brian Bray, Maynard Lichty, Catherine Mader, Gene Merutka
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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: 6008321Abstract: A substrate for solid phase synthesis of the formula: ##STR1## is disclosed. Also disclosed are processes for preparing the substrate and intermediates useful therein. Among the novel intermediates are compounds of the formula: ##STR2## wherein t is 0 or 1; n is 3-20; R is OH, an activated ester or the residue of a solid support having a plurality of amino functionalities; A is --O-- or --NH-- and Q is hydrogen or a protecting group for an amine or alcohol.Type: GrantFiled: March 16, 1998Date of Patent: December 28, 1999Assignee: Pharmacopeia, Inc.Inventors: Ge Li, Sian Louise Griffiths, Edward McDonald, Libo Xu
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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: 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: 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: 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: 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: 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: 5955577Abstract: A method for synthesizing a water-soluble .beta.-sheet forming peptide having at least about 35% amino acids having hydrophobic side chains, the method comprising linking amino acids having charged side chains and amino acids having noncharged polar side chains with amino acids having hydrophobic side chains, wherein the amino acids having charged side chains are provided in a ratio of at least about 2:1 amino acids having positively charged side chains to amino acids having negatively charged side chains; wherein the peptide is water soluble under physiological conditions and forms .beta.-sheet structures.Type: GrantFiled: June 27, 1996Date of Patent: September 21, 1999Assignee: Regents of the University of MinnesotaInventor: Kevin H. Mayo
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Patent number: 5948693Abstract: The present invention relates generally to cyclosporin analogs, and more paritcularly to methods for the solid-phase synthesis and on-resin cyclization of cyclosporin analogs. Methods are described for the on-resin cyclization of sterically hindered compounds synthesized through solid phase synthesis techniques. The methods utilize solvent, temperature, and washing conditions that allow the efficient on-resin cyclization of compounds like analogs of cyclosporin A.Type: GrantFiled: April 14, 1997Date of Patent: September 7, 1999Assignee: Wisconsin Alumni Research FoundationInventors: Daniel H. Rich, Prakash Raman, Yvonne M. Angell