Of Amino Group Patents (Class 530/337)
-
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
-
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
-
Patent number: 5576419Abstract: A triple-helical polypeptide of the formula: ##STR1## is provided wherein: Z is Hyp or Pro; each X and Y is an amino acid such that (Gly-X-Y).sub.m is a sequence of a collagen cell adhesion site; said X and Y may be the same or different and each (Gly-X-Y) may be the same or different; O is an amino acid having a single side-chain amino group; J is an amino acid capable of acting as a chromophore; U is an amino acid; u=0 or 1; n.ltoreq.30; m.ltoreq.30; m+n.ltoreq.30; and j.gtoreq.1. Methods of making these compounds and intermediates used in the methods, are also provided.Type: GrantFiled: September 27, 1995Date of Patent: November 19, 1996Assignee: Regents of the University of MinnesotaInventor: Gregg B. Fields
-
Patent number: 5549883Abstract: A chemically defined polymeric carrier comprising a series of .alpha.-amino acids in any combination containing side chains to which diagnostic/therapeutic and chelating agents can be covalently joined through cleavable linkers either directly or covalently joined through cleavable linkers after chemical modification of the side chains. Hydrazone, disulfide, and ester linkages in any combination can be present in the polymeric carrier between the side chains of the .alpha.-amino acids and the agents. The presence of a particular covalent linkage between the side chain and the agent in the carrier is determined by the functional group present in the side chain of the .alpha.-amino acid and the functional group present in the agent. The .alpha.-amino acids with side chains to which agents do not covalently join can function as spacers to minimize interaction between bulky molecules attached to the polymeric carrier. In addition, those .alpha.Type: GrantFiled: June 3, 1993Date of Patent: August 27, 1996Assignee: NeoRx CorporationInventors: Ananthachari Srinivasan, Vivekananda M. Vrudhula, Diana I. Brixner
-
Patent number: 5545698Abstract: The present invention pertains to polyethylene glycol (PEG) derivatized graft supports, to methods for making these supports and to methods of using the supports to synthesize peptides by solid-phase synthesis techniques. The PEG-graft supports of this invention comprise functionalized PEG derivatives which are covalently attached to solid supports, such as polystyrene.Type: GrantFiled: November 10, 1993Date of Patent: August 13, 1996Assignee: University of MinnesotaInventors: George Barany, Fernando Albericio, Nuria A. Sol e, Jane Chang, Samuel Zalipsky
-
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
-
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
-
Patent number: 5539084Abstract: A method for the separation of at least one specific binding entity from a mixture of binding entities, which comprises the steps of contacting said mixture of binding entities with an immobilized peptide in which said peptide specifically binds to said specific binding entity, and separating the immoblized peptide/specific binding entity complex from the mixture of binding entities; an immobilized peptide-solid support preparation comprising a cleavable link between the peptide and the solid support, and a method for the preparation of a peptide from an immobilized peptide-solid support preparation.Type: GrantFiled: September 6, 1991Date of Patent: July 23, 1996Assignee: Coselco Mimotopes Pty. Ltd.Inventor: Hendrik M. Geysen
-
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
-
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
-
Patent number: 5534497Abstract: The invention relates to a technetium chelate of the general formula ##STR1## wherein X is a sulphur atom or an imino group,Z is a hydrogen atom, a carboxy group, an alkoxycarbonyl group having 1-4 carbon atoms, an aminocarbonyl group, a sulpho group, an aminosulphonyl group or a carboxymethylaminocarbonyl group,Tc represents technetium-99 m,R.sub.1 is a hydrogen atom or an alkyl group having 1 or 2 carbon atoms, andR.sub.2, R.sub.3, R.sub.4 and R.sub.5 are equal or different and represent hydrogen, atoms or branched or non-branched alkyl groups having 1-4 carbon atoms, which alkyl groups are optionally substituted with an amino group, a hydroxy group, a mercapto group, a halogen atom, a carboxy group or an aminocarbonyl group,with the proviso that R.sub.3, R.sub.4 and R.sub.5 do not all three of them represent hydrogen atoms; as well as water-soluble salts of these compounds.Type: GrantFiled: June 4, 1993Date of Patent: July 9, 1996Assignee: Mallinckrodt Medical, Inc.Inventor: Alfons M. Verbruggen
-
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
-
Patent number: 5436221Abstract: A peptide derivative containing 1 to 20 units of peptide unit represented by the following general formula [I] or a pharmaceutically acceptable salt thereof;[Z]--Arg--X--Asp--[Y] [I]wherein Arg represents L- or D-arginine residue, Asp represents L-aspartic acid residue, X represents L- or D-leucine, D-isoleucine, L- or D-norleucine, L- or D-phenylalanine, D-phenylglycine or D-alanine residue, and [Z] and [Y] each represents an amino acid or a peptide residue, which may be present or absent, selected from glycine, L-serine, L-threonine, L- and D-aspartic acid, L-alanine, L- and D-glutamic acid, L-proline residues and a peptide residue constituted by the foregoing amino acid residues, and a pharmaceutical composition comprising the peptide derivative. The composition of the present invention is useful as an agent for inhibiting tumor metastasis.Type: GrantFiled: February 13, 1992Date of Patent: July 25, 1995Assignee: Fuji Photo Film Co., Ltd.Inventors: Hiroshi Kitaguchi, Hiroyuki Komazawa, Masayoshi Kojima, Hideto Mori, Naoyuki Nishikawa, Hideaki Satoh, Atsushi Orikasa, Mitsunori Ono, Ichiro Azuma, Ikuo Saiki
-
Patent number: 5432263Abstract: The present invention provides a process for the preparation of peptides which have or side-chains containing an alkyl- or dialkyl-substituted guanidinyl group or a imidazinylamino or tetrahydropyrimidinylamino group. The process provides higher overall yields of peptide product by permitting the synthesis of the entire peptide chain prior to modification of the side-chain to introduce the groups.Type: GrantFiled: January 28, 1994Date of Patent: July 11, 1995Assignee: Abbott LaboratoriesInventors: Fortuna Haviv, Rolf E. Swenson, Timothy D. Fitzpatrick
-
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
-
Patent number: 5391711Abstract: This invention relates to a biotinylating reagent being used in purification process for synthesis mature peptide. The reagent has at one terminus a functional group capable of forming a bond with the N-terminus amino group of the mature peptide. The bond is stable to the final deprotection reaction under acidic condition at the post-synthesis step of the peptide synthesis process while the bond is specifically cleaved under a difined condition such as basic condition. The reagent also has at the other terminus a biotinyl group. The biotinyl-avidin coupling is used when the reagent modified mature peptide are immobilized selectively on avidin-agarose column. The compounds having following formula (II) are preferable as the reagent.Type: GrantFiled: March 26, 1993Date of Patent: February 21, 1995Assignee: Nihan Millipore Kabushiki KaishaInventors: Susumu Funakoshi, Hiroyuki Fukuda
-
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
-
Patent number: 5300651Abstract: A derivative of tryptophan is provided wherein the NH-group of the tryptophan indole nucleus is protected with tert.-butyloxycarbonyl (BOC) and the .alpha.-amino group is protected by 9-fluorenyl-methyloxy-carbonyl (FMOC). The carboxylic acid group of the tryptophan derivative may comprise a free COOH group, may be modified with a protecting or activating group, or may comprise an acyl group bonded to another chemical moiety, such as a polymer, another amino acid, a dipeptide, a polypeptide, or a protein. The tryptophan derivative is useful in the preparation of dipeptides, polypeptides or proteins containing at least one tryptophan-derived amino acid residue.Type: GrantFiled: May 27, 1992Date of Patent: April 5, 1994Assignee: Calbiochem-Novabiochem AGInventor: Peter D. White
-
Patent number: 5288514Abstract: Methods, compositions, and devices for synthesis of therapeutically useful compounds. The invention provides a rapid approach for combinatorial synthesis and screening of libraries of derivatives of therapeutically important classes of compounds such as benzodiazepines, prostaglandins and .beta.-turn mimetics. In order to expediently synthesize a combinatorial library of derivatives based upon these core structures, general methodology for the solid phase synthesis of these derivatives is also provided. This disclosure thus also describes an important extension of solid phase synthesis methods to nonpolymeric organic compounds.Type: GrantFiled: September 14, 1992Date of Patent: February 22, 1994Assignee: The Regents of the University of CaliforniaInventor: Jonathan A. Ellman
-
Patent number: 5286846Abstract: A new amino derivative, N.sup..alpha. -tert-butoxycarbonyl-N.sup..epsilon. -(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: June 14, 1991Date of Patent: February 15, 1994Assignee: The Government of the United States of America as represented by the Dept. of Health and Human ServicesInventors: John K. Inman, Frank A. Robey
-
Patent number: 5270213Abstract: A method for the generation of phenylthiocarbamyl (PTC) amino acids from phenylthiohydantoin (PTH) or anilinothiozolinone (ATZ) amino acids. The method involves a base-catalyzed ring opening of the PTH or ATZ in the presence of a reducing agent. The method affords an alternative to the established aqueous acid conversion reaction of the Edman degradation in which ATZ and PTC amino acids are converted to the PTH amino acid. A further method is described for the generation of reactive ATZ amino acids from PTH amino acids. These methods facilitate the analysis of protein at low molar amounts by allowing the synthesis of amino acid derivatives which can be analyzed in quantities which are much lower than those required for conventional PTH amino acid analysis.Type: GrantFiled: June 21, 1991Date of Patent: December 14, 1993Assignee: Porton Instruments, Inc.Inventor: Vincent Farnsworth
-
Patent number: 5268423Abstract: A solid phase resin useful as a support for peptide synthesis is synthesized stepwise from a solid phase polymer by reacting a solid phase phenyl ether resin with an alkoxy benzoyl halide to form a solid phase having (alkoxybenzoyl)phenoxymethyl groups bound thereto. The hydroxy group of the benzoyl moiety may be converted to a free amine by reacting with an ammonium salt of a carboxylic acid and then hydrolyzing with alkali. Novel resins produced by this method include those in which the solid phase phenyl ether resin is a resin having alkyl phenyl moieties linked to alkoxy phenyl groups by an ether linkage.Type: GrantFiled: February 28, 1992Date of Patent: December 7, 1993Assignee: New York UniversityInventor: Alvin D. Joran
-
Patent number: 5262331Abstract: A method for monitoring the reaction between an activated carboxylic acid derivative and an amine, such as the formation of a peptide bond in peptide synthesis, whereby an inert anionic dye component and an inert cationic component are included in the reaction system, in small relative amounts compared to the carboxylic acid derivative. The distribution of the dye component to the cationic component, when separated from the amine component, is monitored and at a given maximum value indicates a substantially quantitative reaction.Type: GrantFiled: June 26, 1991Date of Patent: November 16, 1993Inventors: Stephen Salisbury, John Tremeer, David Owen, John Davies
-
Patent number: 5256549Abstract: Oligomers and polymers are prepared substantially free of error sequences by sequentially adding monomers, which are terminally blocked and have active functionalities protected, to a growing chain bound to a support through a selectively cleavable linkage. After each addition, unblocked terminal groups are capped. At the completion of monomer addition, enzymatic hydrolysis interfering protecting groups are removed along with the capping group and failure sequences enzymatically degraded. The terminal blocking group may then be removed. The completed oligomer or polymer may be cleaved from the support prior or subsequent to enzymatic degradation but after completion of the sequence.Type: GrantFiled: April 27, 1990Date of Patent: October 26, 1993Assignee: Chiron CorporationInventors: Michael S. Urdea, Thomas Horn
-
Patent number: 5242974Abstract: A method for cyclization and reversal of the polarity of polymers on a substrate. The method provides for the formation of a polymer on a substrate (2) with a tether molecule (4). Through unmasking of a protective group (PG.sub.2) a cyclic polymer (6) is formed. Through cleavage of an appropriate bond, a polarity reversed polymer (8) is formed. The method finds particular application in the formation of, for example, peptides and oligonucleotides.Type: GrantFiled: November 22, 1991Date of Patent: September 7, 1993Assignee: Affymax Technologies N.V.Inventor: Christopher P. Holmes
-
Patent number: 5240859Abstract: The present invention provides methods and reagents for sequencing amino acids. One embodiment of the method for determining the terminal amino acid of a substantialy pure polypeptide comprises the steps of (a) attaching 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: February 22, 1991Date of Patent: August 31, 1993Assignee: B.R. Centre LimitedInventor: Rudolf H. Aebersold
-
Patent number: 5235028Abstract: The present invention pertains to polyethylene glycol (PEG) derivatized graft supports, to methods for making these supports and to methods of using the supports to synthesize peptides by solid-phase synthesis techniques. The PEG-graft supports of this invention comprise functionalized PEG derivatives which are covalently attached to solid supports, such as polystyrene.Type: GrantFiled: September 16, 1991Date of Patent: August 10, 1993Assignee: University of MinnesotaInventors: George Barany, Fernando Albericio, Jane Chang, Samuel Zalipsky, Nuria A. Sole
-
Patent number: 5191065Abstract: A process for the preparation of tripeptides of the general formula IU-A-B-C-OH Iin which U denotes hydrogen or a urethane protective group and A, B and C denote amino acids, by reaction of a compound of the general formula IIU'-B-OH IIin which U' is a urethane protective group which can be eliminated by hydrogenolysis, with a compound of the general formula IIIH-C-OR IIIin which R denotes alkyl, by the PPA method, elimination of U', and reacting the resulting compound of the formula IVH-B-C-OR IVwith a compound of the formula VU-A-OH Vin the presence of propylphosphonic anhydride, and finally eliminating R enzymatically.Type: GrantFiled: July 8, 1991Date of Patent: March 2, 1993Assignee: Hoechst AktiengesellschaftInventors: Hans-Wolfram Flemming, Manfred Rukwied, Manfred Schmidt
-
Patent number: 5143854Abstract: Polypeptide arrays can be synthesized on a substrate by attaching photoremovable groups to the surface of a substrate, exposing selected regions of the substrate to light to activate those regions, attaching an amino acid monomer with a photoremovable group to the activated regions, and repeating the steps of activation and attachment until polypeptides of the desired length and sequences are synthesized. The resulting array can be used to determine which peptides on the array can bind to a receptor.Type: GrantFiled: March 7, 1990Date of Patent: September 1, 1992Assignee: Affymax Technologies N.V.Inventors: Michael C. Pirrung, J. Leighton Read, Stephen P. A. Fodor, Lubert Stryer
-
Patent number: 5130447Abstract: An improvement is described in the synthesis method for N.sup..alpha. -trityl-N.sup.G -trityl arginine within a process for preparing N.sup..alpha. -fluorenylmethoxycarbonyl-N.sup.G -trityl-arginine from arginine, comprising:a) forming N.sup..alpha. -trityl-N.sup.G -trityl-arginineb) selectively detaching the trityl group from the .alpha.-NH.sub.2 andc) introducing the fluorenylmethoxycarbonyl group in its place.The improvement consists of preparing the N.sup..alpha. -trityl-N.sup.G -trityl-arginine by solubilizing the arginine in an aprotic organic solvent by tri-alkylsilylation both of the amino nitrogen and of the carboxyl group, followed by tritylation, with trityl chloride, of the .alpha.-amino nitrogen, and of the guanidino group after deprotonating this latter with a bicyclic guanidine. The new improved process can also lead to variable quantities of the arginine analogue di-tritylated at the guanidino group, namely N.sup..alpha. -fluorenylmethoxycarbonyl-N.sup.G -di-trityl-arginine.Type: GrantFiled: May 28, 1991Date of Patent: July 14, 1992Assignee: Sclavo S.p.A.Inventors: Valerio Caciagli, Antonio S. Verdini
-
Patent number: 5126273Abstract: A monitoring method for application in solid phase peptide synthesis. In one aspect, the synthesis starts with an amino acid residue protected by an N-alpha-amino protecting group and involves the steps: (a) removing the N-alpha-amino protecting group to obtain an N-alpha-amino group, (b) adding an amino acid residue protected by an N-alpha-amino protecting group, via a peptide bond, to the N-alpha-amino group obtained in step (a) by use of a reactive protected amio acid derivative, and (c) repeating steps (a) and (b). The reaction system includes 3-hydroxy-1,2,3-benzotriazin-4(3H)-one or a derivative thereof; and the color of the reaction system or of a component thereof is monitored during the synthesis.Type: GrantFiled: February 8, 1988Date of Patent: June 30, 1992Assignee: Novobiochem AGInventors: Robert Sheppard, Morten Meldahl
-
Patent number: 5124478Abstract: The invention relates to new compounds of the formula ##STR1## in which R.sup.1 denotes (C.sub.1 -C.sub.8)-alkyl, R.sup.2 denotes an amino acid residue which is protected with a urethane protective group which can be eliminated with weak acid or base, or denotes an amino protective group which can be eliminated with weak acid or base, R.sup.3 denotes hydrogen or (C.sub.1 -C.sub.4)-alkyl, and Y.sup.1 -Y.sup.9 denote identical or different radicals hydrogen, (C.sub.1 -C.sub.4)-alkyl, (C.sub.1 -C.sub.4)-alkoxy or --O--(CH.sub.2).sub.n --COOH (with n=1 to 6), with one of these radicals being --O--(CH.sub.2).sub.n --COOH, or Y.sup.1, Y.sup.2 and Y.sup.5 -Y.sup.9 denote identical or different radicals hydrogen, (C.sub.1 -C.sub.4)-alkyl or (C.sub.1 -C.sub.4)-alkoxy, Y.sup.3 denotes hydrogen or (C.sub.1 -C.sub.8)-alkoxy and Y.sup.4 denotes --(CH.sub.2).sub.n --COOH or --NH--CO--(CH.sub.2).sub.n --COOH (with n=1 to 6).Type: GrantFiled: December 20, 1988Date of Patent: June 23, 1992Assignee: Hoechst AktiengesellschaftInventors: Gerhard Breipohl, Jochen Knolle, Werner Stuber
-
Patent number: 5116947Abstract: A method of synthesis of a partially retro-inverso peptide incorporating at least one malonyl residue of formula (III) ##STR1## wherein R represents the side chain of an .alpha.-amino acid, is described which is characterized in that said malonyl residue is incorporated by condensing a 5-substituted-2,2-dimethyl-1,3-dioxane-4,6-dione of formula (IV) ##STR2## wherein R' is the side-chain R wherein the functional groups, if any, are suitably protected, with an amino acid, amino acid amide, peptide fragment, or pseudo-peptide fragment wherein the terminal carboxyl group, if present, and the possible side-chain functionalities are suitably protected and the reactive amino group is tri-alkyl-silylated.The new compounds of formula (VI) and a process for the preparation of a partially retro-inverso tuftsin analog which involves use of said method and said intermediate are also described and claimed.Type: GrantFiled: August 9, 1991Date of Patent: May 26, 1992Assignee: Sclavo S.p.A.Inventors: Massimo Pinori, Felice Centini, Antonio S. Verdini
-
Patent number: 5115099Abstract: Novel compounds represented by the following formula: ##STR1## wherein A represents a specific amino acid residue are excellent as substrates for determination of enzyme activity such as trypsin, etc. The compounds can be synthesized from novel arginyl-3-tert-alkyloxycarbonyl-4-nitroanilides by a novel process comprising a selective deprotection step whereby the protecting group on the .alpha.-amine group of arginine is removed in the presence of a hydrochloric acid, acetic acid and dimethylformamide mixture, but a tert-alkyl protecting group on the --COOH group of the nitroanilide ring is not removed by this step.Type: GrantFiled: June 13, 1989Date of Patent: May 19, 1992Assignee: Nitto Boseki Co., Ltd.Inventors: Katsumasa Kuroiwa, Hitoshi Matsuura, Katsuhiro Katayama, Shuichi Nakatsuyama, Takeshi Nagasawa, Koji Endo
-
Patent number: 5101059Abstract: This invention relates to compounds of the formula a compound of the formula ##STR1## wherein X is O, CR.sub.7 R.sub.8, S or NR.sub.9 wherein R.sub.7 and R.sub.8 are independently hydrogen, or lower alkyl, and R.sub.9 is lower alkyl;n is 0 or 1;R.sub.1 and R.sub.2 are independently hydrogen, lower alkyl, monoorganosilyl, diorganosilyl, triorganosilyl, halogen, aryl, or nitro;R.sub.3 is hydrogen, lower alkyl, monoorganosilyl, diorganosilyl, triorganosilyl, halogen, 9-fluorenylalkyl, cycloalkyl, aryl or aralkyl;R.sub.4 and R.sub.5 are independently hydrogen, lower alkyl, or aryl or one of R.sub.4 and R.sub.5 is 9-fluorenyl;R.sub.6 is H or COZ wherein Z is an amino acid, a peptide residue or a leaving group; andwith the provisos that when n is 0 and R.sub.3 is hydrogen, R.sub.1 and R.sub.2 are not hydrogen, halogen or nitro; that when n is 0 and R.sub.3 is lower alkyl, R.sub.1 and R.sub.2 are not hydrogen; and that when X is O or CR.sub.7 R.sub.8 wherein R.sub.7 and R.sub.8 are H, that R.sub.1, R.sub.2, R.sub.Type: GrantFiled: December 5, 1989Date of Patent: March 31, 1992Assignee: Research Corporation Technologies, Inc.Inventors: Louis A. Carpino, An-Chuu Wu
-
Patent number: 5079375Abstract: An improvement is described in the synthesis method for N.sup..alpha. -trityl-N.sup.G -trityl arginine within a process for preparing N.sup..alpha. -fluorenyl-methoxycarbonyl-N.sup.G -trityl-arginine from arginine, comprising:a) forming N.sup..alpha. -trityl-N.sup.G -trityl-arginineb) selectively detaching the trityl group from the .alpha.-NH.sub.2 andc) introducing the fluorenylmethoxycarbonyl group in its place.The improvement consists of preparing the N.sup..alpha. -trityl-N.sup.G -trityl-arginine by solubilizing the arginine in an aprotic organic solvent by tri-alkylsilylation both of the amino nitrogen and of the carboxyl group, followed by tritylation, with trityl chloride, of the .alpha.-amino nitrogen, and of the guanidino group after deprotonating this latter with a bicyclic guanidine. The new improved process can also lead to variable quantities of the arginine analogue di-tritylated at the guanidino group, namely N.sup..alpha. -fluorenylmethoxycarbonyl-N.sup.G -di-trityl-arginine.Type: GrantFiled: December 21, 1989Date of Patent: January 7, 1992Assignee: Sclano S.p.A.Inventors: Valerio Caciagli, Antonio S. Verdini
-
Patent number: 5066716Abstract: A method to incorporate bromoacetyl and chloroacetyl moieties on amino groups of synthetic peptides using a standard program with an automated peptide synthesizer has been developed. The bromoacetyl and chloroacetyl-derivatized peptides react well with sulfhydryl-containing proteins and with peptides containing cysteine residues. Autopolymerization or cyclization occurs by reaction of the free sulfhydryl of cysteine in a peptide with the bromoacetyl group (or chloroacetyl group) and reactions can generally be controlled by controlling the concentrations of starting peptide in neutral pH buffers. Analytical methods for evaluating the polymers or cyclized peptides include gel filtration chromatography, reverse phase HPLC, SDS-PAGE and amino acid analysis where the degree of reaction can be evaluated by quantifying the amount of S-carboxymethylcysteine formed after HCl hydrolysis.Type: GrantFiled: December 13, 1988Date of Patent: November 19, 1991Assignee: The United States of America as represented by the Secretary of the Department of Health and Human ServicesInventors: Frank A. Robey, Raymond L. Fields, Wolfgang Lindner
-
Patent number: 5032675Abstract: Improved methods for synthesizing glutamine-containing peptides, involving an active ester method between a protected, C-terminal activated amino acid or a protected, C-terminal activated peptide, and unprotected glutamine in the presence of a weak base, are disclosed.Type: GrantFiled: September 29, 1988Date of Patent: July 16, 1991Assignee: Ajinomoto Co., Inc.Inventors: Toshihisa Kato, Masahiko Kurauchi
-
Patent number: 5028693Abstract: Urethane-protected NCAs and MTAs are prepared by reacting an NCA or NTA with a haloformate in an inert diluent, under anhydrous conditions and in the presence of a tertiary nitrogen-containing base having an atom or functional group sufficiently electron rich and positioned relative to the nitrogen of said base so as to render said atom or group capable of complexing with the H--N< group of said N-carboxyanhydride or N-thiocarboxyanhydride but able to generate N-carboxyanhydride or N-thiocarboxyanhydride anionic complexes capable of reacting with the haloformate.Type: GrantFiled: July 13, 1989Date of Patent: July 2, 1991Assignee: Bioresearch, Inc.Inventors: William D. Fuller, Michael P. Cohen, Fred R. Naider, Murray Goodman
-
Patent number: 5017690Abstract: N-formyl amino acid or peptide is deformylated by reaction with aniline or methylene dianiline over noble metal catalyst, e.g., Pt-on-carbon. N-formanilide is formed as by-product. The process is particularly useful in deformylating N-formyl aspartame.Type: GrantFiled: August 11, 1989Date of Patent: May 21, 1991Assignee: W. R. Grace & Co.-Conn.Inventor: Jennifer M. Quirk
-
Patent number: 5008372Abstract: Deblocking of amino terminal N-acetyl serine and N-acetyl threonine residue in proteins and peptides to allow sequencing by the Edman degradation technique is carried out by reacting blocked protein or peptide with anhydrous trifluoracetic acid for 1 to 15 minutes at 30.degree. to 60.degree. C., removing the remaining trifluoroacetic acid and maintaining reacting mixture from which trifluoroacetic acid has been removed at 30.degree. to 100.degree. C. for 60 minutes to 5 days.Type: GrantFiled: February 12, 1990Date of Patent: April 16, 1991Assignee: Cornell Research Foundation, Inc.Inventor: Daniel Wellner
-
Patent number: 4963653Abstract: A sialic acid-bonded octapeptide represented by the following general formula (I): ##STR1## wherein R represents a hydrogen atom or an acetyl group; and R' represents a lower alkyl group, an aralkyl group, a hydrogen atom or an alkali metal atom, is herein disclosed. The peptide chain of the sialic acid-bonded octapeptide is constituted by 8 amino acid molecules on the C-terminus side of FTS and the compounds represented by formula (I) can be obtained by bonding sialic acid to the amino terminus of the peptide chain according to condensation. These octapeptides show excellent physiological activity comparable to FTS and a half life in blood longer than that of FTS and it is expected that the affinity of the peptide to lymphocytes is also enhanced. Thus they can effectively be used as medicines for treating the lowering and abnormality of functions of the thymus.Type: GrantFiled: June 28, 1989Date of Patent: October 16, 1990Assignees: Mect Corporation, Mitsui Toatsu Chemical, Inc.Inventors: Yoshitaka Nagai, Shohei Shibayama, Masaaki Numata, Shoji Yoshimura, Makoto Tanaka, Masayoshi Ito, Akira Awaya, Hisashi Kobayashi, Hayao Abe, Yusaku Ishizuka, Tomoya Ogawa
-
Patent number: 4946942Abstract: The invention relates to urethane-protected amino acid-N-carboxyanhydride and N-thiocarboxyanhydride compounds which are useful in peptide, polypeptide and protein synthesis. Disclosed herein is the preparation and use of these novel compounds.Type: GrantFiled: March 11, 1988Date of Patent: August 7, 1990Assignee: Bioresearch, Inc.Inventors: William D. Fuller, Michael P. Cohen, Fred R. Naider, Murray Goodman
-
Patent number: 4923966Abstract: Use of a guanidine-related compound in solution phase peptide synthesis, the guanidine-related compound comprising a tetraphenylborate ion and having the general formula: ##STR1## wherein R denotes an organic radical comprising at least one amine group.Type: GrantFiled: June 17, 1988Date of Patent: May 8, 1990Assignee: Solvay & Cie (Societe Anonyme)Inventors: Roland Callens, Andre Collin
-
Patent number: 4922015Abstract: The invention relates to new compounds of the formula ##STR1## in which R.sup.1 denotes (C.sub.1 -C.sub.8)-alkyl or optionally substituted (C.sub.6 -C.sub.14)-aryl, R.sup.2 denotes hydrogen or an amino acid residue which is protected by an amino protective group which can be cleaved off with weak acid or base, R.sup.3 denotes hydrogen or (C.sub.1 -C.sub.4)-alkyl, and Y.sup.1 -Y.sup.9 denote identical or different radicals hydrogen, (C.sub.1 -C.sub.4)-alkyl, (C.sub.1 -C.sub.4)-alkoxy or -O-(CH.sub.2).sub.n -COOH (with n=1 to 6), one of these radicals being -O-(CH.sub.2).sub.n -COOH. A process for the preparation thereof and the synthesis of peptide amides by means of a solid phase method using these new compounds (spacers) are described.Type: GrantFiled: April 6, 1988Date of Patent: May 1, 1990Assignee: Hoechst AktiengesellschaftInventors: Gerhard Breipohl, Jochen Knolle, Werner Stuber
-
Patent number: 4826816Abstract: Antihypertensive compounds with angiotensin-converting enzyme inhibitory activity and diuretic activity are disclosed. Such compounds are useful in the treatment of cardiovascular disorders, especially hypertension and congestive heart failure, and are useful in the treatment of glaucoma.Type: GrantFiled: October 4, 1985Date of Patent: May 2, 1989Assignee: Schering CorporationInventors: David R. Andrews, Federico C. A. Gaeta
-
Patent number: 4755558Abstract: A method is provided for quantitatively monitoring the deprotection and coupling reactions employed in the solid phase synthesis of peptides. The method entails synthesizing a peptide on a support matrix that has a first marker associated therewith. The amino acids employed in the peptide synthesis procedure have a second marker attached thereto, which can be the blocking group used for the amino acid. After the coupling or deprotection step a portion of the support matrix is processed to release first and second identifers from the first and second markers, respectively. The completeness of the coupling or deprotection step can be determined by comparing the relative amounts of the detected first and second identifiers. Novel compositions of matter are used in or produced during this method, including support matrixes having pyrolyzable markers attached thereto.Type: GrantFiled: May 30, 1986Date of Patent: July 5, 1988Assignee: Beckman Instruments, Inc.Inventor: Suresh M. Kalbag
-
Patent number: 4714768Abstract: A new compound is disclosed, N-(chlorocarbonyloxy-5-norbornene-2,3-dicarboximide I, in addition to processes for its production and employment of the compound as starting product for the manufacture of non-symmetrical carbonate, urethane-protected amino acid or peptide, activated carrier and carrier-ligand-complexes. The new compound is reacted with alcohols as well as with hydroxyl-group-containing or amino-group-containing polymers.Type: GrantFiled: August 27, 1984Date of Patent: December 22, 1987Assignee: Akademie Der Wissenschaften Der DDRInventors: Peter Henklein, Manfred Becker, Werner Buttner, Fritz Loth, Horts Dautzenberg, Klaus Forner, Rudolf Dolling, Karl-Heinz Graul, Wolf-Rainer Halatsch, Christian Rupprich
-
Patent number: 4638045Abstract: A novel bioerodible polymeric composition is provided comprising a plurality of monomer units of two or three amino acids which are polymerized via hydrolytically labile bonds at their respective side chains rather than at the amino or carboxylic acid terminals by amide bonds. Such polymers are useful for controlled release applications in vivo and in vitro for delivery of a wide variety of biologically and pharmacologically active ligands.Type: GrantFiled: February 19, 1985Date of Patent: January 20, 1987Assignee: Massachusetts Institute of TechnologyInventors: Joachim Kohn, Robert S. Langer