Protecting Or Removing Protective Groups, E.g., Carboxyl Group Protection, Etc. Patents (Class 530/335)
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Patent number: 5917015Abstract: A support material for solid phase synthesis is provided having an amine-containing organic group attached to it through a linker.Type: GrantFiled: June 18, 1996Date of Patent: June 29, 1999Assignee: Regents of the University of MinnesotaInventors: Knud J. Jensen, George Barany, Micheal F. Songster, Fernando Albericio, Jordi Alsina, Josef Vagner
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Patent number: 5869605Abstract: The protective group having the following formula (I):Ar--L-- (I)whereinAr represents a substantially planar, fused ring system containing at least 4 aromatic rings, andL represents a group containing at least one carbon atom which is capable of bonding to a group to be protected.Type: GrantFiled: August 11, 1994Date of Patent: February 9, 1999Assignee: Rhone-PoulencChimieInventors: Robert Ramage, Gilles Raphy
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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: 5859190Abstract: The invention provides a rapid approach for combinatorial synthesis and screening of libraries of hydantoin and thiohydantoin compounds. The present invention further provides the compounds made by the combinatorial synthesis.Type: GrantFiled: February 4, 1997Date of Patent: January 12, 1999Assignee: Trega Biosciences, Inc.Inventors: Jean-Philippe Meyer, John M. Ostresh, Richard A. Houghten
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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: 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: 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: 5837807Abstract: This invention is directed to tetrahydronaphthalene compounds of the formula ##STR1## wherein R.sup.1 is hydrogen, bromine, cyano, formyl, hydroxy, lower alkyl, lower alkenyl, lower alkynyl, lower alkoxy, aryloxy, lower aralkoxy or aryl; R.sup.2 is an amino acid residue or a chain of 2 to 20 amino acid residues wherein reactive moieties in the side chains of the amino acid residue(s) is/are protected or unprotected, and wherein the amino group of the N-terminal amino acid is a free or protected amino group; A.sup.1, A.sup.2, A.sup.3 and A.sup.4 each are .alpha.-amino acid residues wherein A.sup.1 and A.sup.2 are in the L configuration and A.sup.3 and A.sup.4 are in the D configuration when the .alpha.-C atom of said .alpha.-amino acid residue is asymmetric; X is oxygen or sulphur; Y is a residue of the formula ##STR2## n is 0 or 1; R.sup.3 is hydrogen or lower alkyl; R.sup.Type: GrantFiled: February 27, 1996Date of Patent: November 17, 1998Assignee: Hoffmann-La Roche Inc.Inventors: Christine Abrecht, Alfred Grieder, Klaus Muller, Daniel Obrecht
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Patent number: 5831070Abstract: A method and apparatus for selectively applying a print material onto a substrate for the synthesis of an array of oligonucleotides at selected regions of a substrate. The print material includes a barrier material, a monomer sequence, a nucleoside, a deprotection agent, a carrier material, among other materials. The method and apparatus also relies upon standard DMT based chemistry, and a vapor phase deprotection agent such as solid TCA and the like.Type: GrantFiled: April 19, 1996Date of Patent: November 3, 1998Assignee: Affymetrix, Inc.Inventors: R. Fabian Pease, Glenn McGall, Martin J. Goldberg, Richard P. Rava, Stephen P. A. Fodor, Virginia Goss, Lubert Stryer, James L. Winkler
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Patent number: 5814700Abstract: A method of synthesis for building a polymer chain, oligonucleotides in particular, by sequentially adding monomer units to at least one solid support for growing and immobilizing a polymer chain thereon in a liquid reagent solution. The method includes the step of: A) depositing a liquid reagent in a reaction well (26) in contact with at least one solid support and at least one monomer unit of the polymer chain affixed to the solid support. The well (26) includes at least one orifice (74) extending into the well (26), and is of a size and dimension to form a capillary liquid seal to retain the reagent solution in the well (26) to enable polymer chain growth on the solid support. The method further includes the step of B) expelling the reagent solution from the well (26), while retaining the polymer chain therein.Type: GrantFiled: May 30, 1995Date of Patent: September 29, 1998Assignee: The Board of Trustees of the Leland Stanford Junior UniversityInventor: Thomas M. Brennan
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Patent number: 5807986Abstract: Compounds termed "betides" mimic peptides and contain one or more residues of aminoglycine, C.sup..alpha. -aminoalanine, aminosarcosine or the like wherein the side chain amino group has been acylated and optionally also alkylated. Generally, betides have the formula: X.sub.N -X.sub.1 -X.sub.2 -X.sub.3 -X.sub.m -X.sub.4 -X.sub.5 -X.sub.6 -X.sub.C, where X.sub.N is an acyl or other N-terminal group or a peptide up to about 50 amino acids in length having such a group; X.sub.C is OH, NH.sub.2 or other C-terminal group or a peptide up to about 50 amino acids in length having such a group; and X.sub.1 -X.sub.6 are each independently a betidamino acid or .alpha.-amino acid or des-X; and X.sub.m is a peptide up to about 50 amino acids or des-X; provided however that at least one of X.sub.1 -X.sub.6 is a betidamino acid residue having the formula: ##STR1## wherein R.sub.0 is H or CH.sub.3, R and R.sub.2 are H or lower alkyl, and R.sub.Type: GrantFiled: December 28, 1995Date of Patent: September 15, 1998Assignee: The Salk Institute For Biological StudiesInventors: Jean E. F. Rivier, John S. Porter
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Patent number: 5798444Abstract: 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: September 5, 1996Date of Patent: August 25, 1998Inventors: T. Jeffrey Dunn, Ananthachari Srinivasan
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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: 5767239Abstract: The invention relates to a process for the preparation of cardiodilatin fragments, to highly purified cardiodilatin fragments, and to appropriate intermediates for the preparation of said fragments. Furthermore, the invention relates to highly purified cardiodilatin fragments which are free of peptide impurities and exhibit a single migration peak in capillary electrophoresis, as well as to appropriate processes for the preparation of same.Type: GrantFiled: December 2, 1996Date of Patent: June 16, 1998Assignee: Boehringer Mannheim GmbHInventors: Hansueli Immer, Wolf-Georg Forssmann, Knut Adermann, Christian Klessen
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Patent number: 5763170Abstract: A method for forming and using an array of, e.g., bacteria, yeast or bacteriophage for the purpose of identifying particular constituents thereof. The array is formed by directing a stream of droplets, each containing on average about 1 or a few biological particles, at spaced locations in an array on a surface, e.g., a nylon membrane or agar gel.Type: GrantFiled: June 5, 1995Date of Patent: June 9, 1998Assignee: Amersham International plcInventor: Margaret Raybuck
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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: 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: 5712367Abstract: A process is disclosed for making peptides soluble in a water-immiscible organic solvent, comprising linking a lipophilic group with an amide or ester bond to the terminal carboxyl group of said peptide; when the lipophilic group is linked to L-serine, a molecule is obtained with a solubility in water at 25.degree. C. of less than 30 g/liter. This lipophilic group is non-polymeric and chemically defined. A process is also disclosed for the synthesis of peptides, optionally protected, in a liquid medium, wherein the starting material is an amino acid or peptide made soluble in an organic medium by a lipophilic group A--L linked to the carboxyl function of the starting amino acid or peptide, and are added to amino acids or peptides to be condensed which are activated on their acid function and protected on their amine function and are optionally protected on their side chain.Type: GrantFiled: October 25, 1994Date of Patent: January 27, 1998Assignee: Rhone-Poulenc ChimieInventors: Jean-Marie Bernard, Kamel Bouzid, Christian Gervais
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Patent number: 5710249Abstract: Methods of making unnatural amino acids are provided which unnatural amino acids can be incorporated into peptides which either inhibit or promote the secretion of gonadotropins by the pituitary gland and inhibit the release of steroids by the gonads. These unnatural amino acids are useful in the synthesis of peptides and have the formula (a): ##STR1## where W is (CH.sub.2) or ##STR2## n is an integer from 1 to 6; j=1, 2 or 3, and preferably, Y is N--CN, X is NH and R.sub.2 is alkyl, modified alkyl, alkenyl, alkynyl, aryl or methyl pyridyl. Disclosed are peptides that 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: June 6, 1995Date of Patent: January 20, 1998Assignee: The Salk Institute for Biological StudiesInventors: Carl A. Hoeger, Jean E. F. Rivier, John S. Porter
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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: 5677195Abstract: A method and device for forming large arrays of polymers on a substrate (401). According to a preferred aspect of the invention, the substrate is contacted by a channel block (407) having channels (409) therein. Selected reagents are delivered through the channels, the substrate is rotated by a rotating stage (403), and the process is repeated to form arrays of polymers on the substrate. The method may be combined with light-directed methodolgies.Type: GrantFiled: November 20, 1992Date of Patent: October 14, 1997Assignee: Affymax Technologies N.V.Inventors: James L. Winkler, Stephen P. A. Fodor, Christopher J. Buchko, Debra A. Ross, Lois Aldwin, Douglas N. Modlin
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Patent number: 5665861Abstract: Described is a peptide fragment which comprises the amino acid sequence 95-126 of ANF/CDD 1-126 (gamma-hANaP) and is formed in the kidney. The fragment urodilatin (ANF/CDD 95-126) has the following amino acid sequence: ##STR1## wherein R.sup.1 and R.sup.2 each represent further peptide fragments of ANF/CDD 1-126 (gamma-hANaP). In the amino acid sequence R.sup.1 is Thr-Ala-Pro-Arg-Ser-Leu-Arg-Arg-Ser-Ser and R.sup.2 is Asn-Ser-Phe-Arg-Tyr. Further described are processes for the preparation and/or recovery of the new peptide fragment and a medicament containing urodilatin (ANF/CDD 95-126) as well as medical indications of the medicament.Type: GrantFiled: June 7, 1995Date of Patent: September 9, 1997Assignee: HaemoPep Pharma GmbHInventors: Wolf-Georg Forssmann, Jeanette M. Alt, Gerhard Becker, Franz Herbst
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Patent number: 5658734Abstract: The present invention relates to a process for synthesizing on a single substrate a plurality of chemical compounds having diverse structures. The process involves the use of a bilayer photoresist to build up selected regions of the array in a step wise fashion.Type: GrantFiled: October 17, 1995Date of Patent: August 19, 1997Assignee: International Business Machines CorporationInventors: Phillip Joe Brock, William Dinan Hinsberg, Jeffrey William Labadie, Glenn McGall, Gregory Michael Wallraff
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Patent number: 5639603Abstract: A general stochastic method for synthesizing compounds can be used to generate large collections of tagged compounds that can be screened to identify and isolate compounds with useful properties.Type: GrantFiled: November 2, 1993Date of Patent: June 17, 1997Assignee: Affymax Technologies N.V.Inventors: William J. Dower, Ronald W. Barrett, Mark A. Gallop, Michael C. Needels
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Patent number: 5624711Abstract: Methods and derivatized supports which are useful in solid-phase synthesis of peptides, oligonucleotides or other small organic molecules as well as arrays of ligands. The methods provide means to control the functional site density on a solid support. Some of the derivatized supports are polymer-coated or glycan-coated. Other methods for regenerating the surface of a used ligand array are also provided.Type: GrantFiled: April 27, 1995Date of Patent: April 29, 1997Assignee: Affymax Technologies, N.V.Inventors: Steven A. Sundberg, David Fujimoto
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Patent number: 5616327Abstract: Peptides substantially corresponding to the 148-162 region of type A influenza M protein and additionally containing at least one amino acid in the 163-166 region are disclosed to have high activity as influenza transcription inhibitors and thus as antiviral agents against influenza virus and other RNA viruses. The modification of these peptides by incorporation into liposomes or by addition of long-chain alkylamino acids is also shown as in the use of all such materials in antiviral drug formulations.Type: GrantFiled: November 7, 1994Date of Patent: April 1, 1997Assignees: SRI International, New York Medical CollegeInventors: Amrit K. Judd, Doris J. Bucher
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Patent number: 5599695Abstract: A method and apparatus for selectively applying a print material onto a substrate for the synthesis of an array of oligonucleotides at selected regions of a substrate. The print material includes a barrier material, a monomer sequence, a nucleoside, a deprotection agent, a carrier material, among other materials. The method and apparatus also relies upon standard DMT based chemistry, and a vapor phase deprotection agent such as solid TCA and the like.Type: GrantFiled: February 27, 1995Date of Patent: February 4, 1997Assignee: Affymetrix, Inc.Inventors: R. Fabian Pease, Glenn McGall, Martin J. Goldberg, Richard P. Rava, Stephen P. A. Fodor, Virginia Goss, Lubert Stryer, James L. Winkler
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Patent number: 5591646Abstract: Method and apparatus for simple and rapid preparation of reusable, addressable surface-immobilized arrays of biomolecules (libraries) used for screening for interaction with any biologically significant target. A special plate having on its surface a plurality of discreet functionalized substrate areas, typically in arrays of 10.times.10 to 400.times.400, is provided for chemical synthesis or bonding thereon of desired families of biomolecules (e.g. peptides, DNA, RNA, oligosaccharides). In the case of peptides, such as hexapeptides, the resulting permanently hexapeptide-loaded plate is a reusable Addressable Synthetic Peptide Combinatorial Library (ASPCL), in which 1 to 3 (typically two) of the positions in the sequence are uniquely identified by the address location. Plate embodiments include substrates of physically bonded (e.g.Type: GrantFiled: September 2, 1992Date of Patent: January 7, 1997Assignee: Arris PharmaceuticalInventors: Derek Hudson, Charles R. Johnson, Lutz Giebel
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Patent number: 5580957Abstract: 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: March 18, 1994Date of Patent: December 3, 1996Assignee: The Salk Institute for Biological StudiesInventors: Carl A. Hoeger, Jean E. F. Rivier, Paula G. Theobald, John S. Porter
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Patent number: 5541114Abstract: A method for sequencing proteins on a polytetrafluoroethylene support is described. The support is preferably porous. The sample to be sequenced may be transferred directly, e.g., by blotting, to the support. Covalent binding of the sample to the support is not required.Type: GrantFiled: March 15, 1994Date of Patent: July 30, 1996Assignee: City of HopeInventors: Jerome M. Bailey, John E. Shively
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Patent number: 5541314Abstract: Apparatus and method for the automated synthesis of DNA segments utilizing multiple reaction columns, all of which are open at the inlet end to the atmosphere of a reaction chamber. A movable reagent supply line outlet is positioned adjacent to the column inlet end to apply reagent to each of the columns according to an input sequence of delivery. The delivery sequence is under processor control. Reagents are removed from all columns simultaneously through the application of vacuum at the outlet end of each column. The device enables the parallel synthesis of large numbers of different oligonucleotide sequences of different lengths.Type: GrantFiled: August 2, 1994Date of Patent: July 30, 1996Assignee: University of Georgia Research Foundation, Inc.Inventors: Royal A. McGraw, William M. Grosse
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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
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Patent number: 5536815Abstract: The present invention is directed to the use of a cyclopropylmethyl derivative as a protecting group for compounds containing an amino group, carboxy group, amido group, mercapto group or hydroxy group and to the compounds formed having the cyclopropylmethyl moiety as the protecting group.Type: GrantFiled: March 31, 1994Date of Patent: July 16, 1996Assignee: Research Corporation Technologies, Inc.Inventors: Louis A. Carpino, Hann-Guang Chao
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Patent number: 5534440Abstract: The present invention provides methods and reagents for sequencing amino acids. One embodiment of the method for determining the terminal amino acid of a polypeptide comprises the steps of (a) attaching (either covalently or non-covalently) the polypeptide to a solid support, (b) reacting the polypeptide with a compound described below, under conditions and for a time sufficient for coupling to occur between the terminal amino acid of the polypeptide and the compound, thereby yielding a polypeptide with a derivatized terminal amino acid, (c) washing the solid support to remove unbound material, (d) cleaving the derivatized terminal amino acid from the polypeptide with a cleaving agent, (e) ionizing the cleaved derivatized terminal amino acid, and (f) determining the molecular weight of the derivatized terminal amino acid, such that the terminal amino acid is determined.Within one embodiment, the compound is p-isothiocyanato phenethyl trimethylammonium and counterion salts thereof.Type: GrantFiled: August 30, 1993Date of Patent: July 9, 1996Assignee: Biomedical Research Centre LimitedInventors: Rudolf H. Aebersold, Edward J. Bures
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Patent number: 5453488Abstract: The invention concerns novel renin-inhibitory compounds which contain an amino-substituted heterocycle at the P.sub.2 position. These are useful for treating renin-associated hypertension, congestive heart failure, glaucoma, hyperaldosteronism, and diseases caused by retroviruses including HTLV-I and -III. Processes for preparing the compounds, compositions containing them, and methods of using them are included. Also included is a diagnostic method which uses the compounds to determine the presence of renin-associated hypertension, or hyperaldosteronism.Type: GrantFiled: March 26, 1993Date of Patent: September 26, 1995Assignee: Warner-Lambert CompanyInventors: Cleo Connolly, Annette M. Doherty, Harriet W. Hamilton, William C. Patt, Ila Sircar
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Patent number: 5444150Abstract: A new amino acid derivative, N.sup..alpha. -tert-butoxycarbonyl-N.sup.e -(N-bromoacetyl-.beta.-alanyl)-L-lysine (BBAL), has been synthesized as a reagent to be used in solid-phase peptide synthesis for introducing a side-chain bromoacetyl group at any desired position in a peptide sequence. The bromoacetyl group subsequently serves as a sulfhydryl-selective cross-linking function for the preparation of cyclic peptides, peptide conjugates and polymers. BBAL residues are stable to final HF deprotection/cleavage. BBAL peptides can be directly coupled to other molecules or surfaces which possess free sulfhydryl groups by forming stable thioether linkages. Peptides containing both BBAL and cysteine residues can be self-coupled to produce either cyclic molecules or linear peptide polymers. Such peptide derivatives are useful in preparing potential peptide immunogens, vaccines and therapeutics, and for substances such as peptides linked to polymers, plastics, enamels and ceramics.Type: GrantFiled: November 19, 1993Date of Patent: August 22, 1995Assignee: The United States of America as represented by the Department of Health and Human ServicesInventors: John K. Inman, Frank A. Robey
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Patent number: 5405783Abstract: A technique for the synthesis of arrays of diverse polymers such as polypeptides and nucleic acids. The technique beneficially utilizes solid-phase chemistry techniques. Preferred embodiments utilize photolabile protecting groups, and photolithography. The technique forms polymers with monomer sequences and locations determined by the order of addition of monomers and the activation patterns formed on the substrate.Type: GrantFiled: March 12, 1992Date of Patent: April 11, 1995Assignee: Affymax Technologies N.V.Inventors: Michael C. Pirrung, J. Leighton Read, Stephen P. A. Fodor, Lubert Stryer
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Patent number: 5384261Abstract: A method and device for forming large arrays of polymers on a substrate (401). According to a preferred aspect of the invention, the substrate is contacted by a channel block (407) having channels (409) therein. Selected reagents are flowed through the channels, the substrate is rotated by a rotating stage (403), and the process is repeated to form arrays of polymers on the substrate. The method may be combined with light-directed methodolgies.Type: GrantFiled: November 22, 1991Date of Patent: January 24, 1995Assignee: Affymax Technologies N.V.Inventors: James L. Winkler, Stephen P. A. Fodor, Christopher J. Buchko, Debra A. Ross, Lois Aldwin
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Patent number: 5366871Abstract: A method for assaying for enzymes that modify peptide chains, such as protein kinases and enzymes which modify the C-terminus of the Ha-RAS protein, is defined. This is done by incubating an extract in which the enzyme being assayed for may be present contained in a reaction mixture. The reaction mixture is made up of a buffer solution, a ubiquitin peptide extension, wherein the peptide contains a sequence known to be modified by an agent in the presence of the enzyme being assayed for, and the agent known to modify the peptide extension when the enzyme is present. The incubation is stopped and the ubiquitin peptide extension is separated from the solution and analyzed for the presence of the agent modified peptide. The extent of peptide modification can be both qualitative and quantative of the enzyme being assayed for. Protein kinases can be assayed for using a ubiquitin pepide extension containing the sequence (SEQ ID NO:1), Ser-Glu-Glu-Glu-Glu-Glu in the presence of a phosphorylating agent.Type: GrantFiled: November 13, 1991Date of Patent: November 22, 1994Assignee: The University of UtahInventors: Martin C. Rechsteiner, Yung J. Yoo
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Patent number: 5360928Abstract: A compound of the formula ##STR1## or the acid fluoride salts thereof wherein BLK is an N-amino protecting group or hydrogenAA is an amino acid residue andX is H or a protecting group useful as a coupling agent in peptide synthesis.Type: GrantFiled: October 23, 1989Date of Patent: November 1, 1994Assignee: Research Corporation Technologies, Inc.Inventors: Louis A. Carpino, Dean Sadat-Aalaee
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Patent number: 5357043Abstract: The invention relates to a process for the preparation of an oligopeptide or amino acid alkyl ester.HCl salt, the alkyl group being methyl, ethyl, isopropyl or n-propyl, by converting an oligopeptide.HCl salt or amino acid.HCl salt with an alkanol corresponding to the alkyl group under the influence of an acid catalyst, 0.01-0.5 mol HCl relative to the oligopeptide.HCl salt or amino acid.HCl salt in combination with an acid ion exchange resin being used as acid catalyst.Type: GrantFiled: December 18, 1992Date of Patent: October 18, 1994Assignee: Holland Sweetener Company V.O.V.Inventors: Hubertus J. A. V. Delahaye, Johan T. Tinge, Adelbert A. H. Drinkenburg, Antonius J. J. M. Teunissen, Willem Klop
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Patent number: 5322931Abstract: A solution phase process for making peptides having biological activity or peptide intermediates which can be used to prepare peptides having biological activity is described. The process involves the condensation reaction of two peptide fragments.Type: GrantFiled: October 22, 1992Date of Patent: June 21, 1994Assignee: Eastman Kodak CompanyInventors: John C. Hubbs, Stephen W. Parker
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Patent number: 5304470Abstract: Protected and unprotected di- or oligopeptides are synthesized by reacting an N-terminally protected .alpha.-amino acid alkyl ester or peptide alkyl ester of the formula X--E--R.sup.1 with an amino acid or a di- or oligopeptide or a derivative thereof of the formula H.sub.2 N--Q--R.sup.2 in aqueous solution in the presence of a hydrolase, and, removing protective groups from the reaction product separated from the reaction mixture, where E is the residue of an .alpha.-amino acid or of a di- or oligopeptide, R.sup.1 is lower alkyl and X is a group which carries a charge or is polar at the pH values used for the reaction and which increases the solubility by a factor >5 compared with compounds wherein X=H, Q is the residue of an amino acid or of a di- or oligopeptide, and R.sup.2 is an optionally esterified or amidated acid group. In a preferred embodiment, the peptide or (.alpha.Type: GrantFiled: January 23, 1992Date of Patent: April 19, 1994Assignees: Forschungszentrum Juelich GmbH, Degussa AGInventors: Andreas Fischer, Alexander Schwarz, Christian Wandrey, Guenter Knaup, Andreas Bommarius, Karl-Heinz Drauz