Solution Phase Synthesis Patents (Class 530/338)
  • Patent number: 9029504
    Abstract: Particular compounds having a fluorene skeleton are superior in broad utility and stability, as a protecting reagent for liquid phase synthesis of amino acids and/or peptides.
    Type: Grant
    Filed: September 16, 2013
    Date of Patent: May 12, 2015
    Assignee: Ajinomoto Co., Inc.
    Inventor: Daisuke Takahashi
  • Patent number: 8969524
    Abstract: The present invention is related to peptides that can be used to reduce the immune response against FVIII or to induce tolerance to human FVIII in patients with, e.g., hemophilia A. Furthermore, the peptides can be used for immunodiagnostic purposes to detect FVIII-specific CD4+ T cells to monitor patients with hemophilia A during replacement therapy and during immune tolerance induction therapy.
    Type: Grant
    Filed: October 27, 2011
    Date of Patent: March 3, 2015
    Assignees: Baxter International Inc., Baxter Healthcare SA
    Inventors: Katharina Nora Steinitz, Paula Maria Wilhelmina van Helden, Birgit Maria Reipert, Hans-Peter Schwarz, Hartmut Ehrlich
  • Patent number: 8877892
    Abstract: We describe methods that allow either carbodiimides or other carboxyl-reactive substances to be mixed with solutions of carboxylic acids or phosphates or amines or combinations thereof, so as to form a homogeneous mixture which is then dried, preferably in a freeze drying process. The mixture is then contacted with an entity, which preferably involves the dissolution of the mixture with a buffered solution of the entity, so as to initiate a conjugation reaction between the entity and a component in the mixture.
    Type: Grant
    Filed: March 15, 2011
    Date of Patent: November 4, 2014
    Assignee: Innova Biosciences Limited
    Inventors: Nicholas Gee, Annamaria Draghi
  • Patent number: 8784777
    Abstract: A solid phase peptide synthesis method for synthesizing a peptidyl contrast agent is disclosed. In one example, the method includes synthesizing an amino-chelator loaded resin, coupling of the amino-chelator loaded resin to the C-terminus and/or backbone of a peptide, cleaving the amino-chelator-peptide from a resin, and chelating a lanthanide metal to the amino-chelator-peptide.
    Type: Grant
    Filed: November 29, 2010
    Date of Patent: July 22, 2014
    Assignee: Case Western Reserve University
    Inventors: Mark D. Pagel, Byunghee Yoo
  • Publication number: 20140128572
    Abstract: A process for extraction of a peptide from a reaction mixture resulting from a peptide coupling reaction, the reaction mixture containing the peptide and a polar aprotic solvent selected from N,N-dimethylformamide, N,N-dimethylacetamide and N-methyl-2-pyrrolidone, whereby the process includes a step a) and a step b): step a) including the addition of a component a1), a component a2) and a component a3), whereby component a1) is an organic solvent 1, the organic solvent 1 is selected from 2-methyltetrahydrofuran and toluene, component a2) is water, and component a3) is an organic solvent 2, the organic solvent 2 is selected from the ethylacetate, isopropylacetate, acetonitrile, tetrahydrofuran and n-heptane to the reaction mixture, so that a biphasic system with an organic layer and an aqueous layer is obtained; step b) including the subsequent separation of the organic layer containing the peptide from the aqueous layer.
    Type: Application
    Filed: June 14, 2012
    Publication date: May 8, 2014
    Applicants: Lonza Braine S.A., Lonza Ltd
    Inventors: Didier Monnaie, Luciano Forni, Mathieu Giraud
  • Patent number: 8716439
    Abstract: The present invention is related to a method of producing a peptide, characterized in contacting a reaction mixture with a base after a condensation reaction to hydrolyze while a basic condition is maintained until a ratio of a remaining unreacted active ester of an acid component is decreased to 1% or less in a liquid phase peptide synthesis method. According to the invention, a target peptide of high purity can be simply and efficiently produced by a continuous liquid phase synthesis method. Further, the present invention is related to a method of producing a peptide, characterized in using an amide-type solvent immiscible with water in a liquid phase peptide synthesis method. According to the invention, various peptides can be produced by the liquid phase synthesis method without being restricted by the amino acid sequence of the target peptide.
    Type: Grant
    Filed: July 31, 2006
    Date of Patent: May 6, 2014
    Assignee: Kaneka Corporation
    Inventors: Hiroshi Murao, Ken-ichiro Morio, Masaru Mitsuda
  • Publication number: 20140107023
    Abstract: The present invention relates to a non-peptidyl polymer-insulin multimer comprising two or more of a non-peptidyl polymer-insulin conjugate prepared by linking a non-peptidyl polymer and insulin via a covalent bond, in which the conjugates are complexed with cobalt ion to form a multimer, a method and kit for the preparation of the multimer, a pharmaceutical composition for the prevention or treatment of diabetes comprising the multimer as an active ingredient, and a method for preventing or treating diabetes by administering the composition to a subject.
    Type: Application
    Filed: June 1, 2012
    Publication date: April 17, 2014
    Applicant: HANMI SCIENCE CO., LTD
    Inventors: Sung In Lim, Myung Hyun Jang, Dae Jin Kim, Sung Youb Jung, Se Chang Kwon
  • Patent number: 8691941
    Abstract: Peptides may be produced by using (A) a first amino acid or peptide, which is converted into its ionic liquid form through the formation of an ionic bond, as a substance serving as both a reaction solvent and a reaction starting material; and reacting the first amino acid or peptide with (B) an ester of second amino acid or peptide, in the absence of any peptide hydrolase or any condensation agent, in the presence of water in an amount of not more than 20% by mass relative to the total mass of the reaction system to form a peptide bond between the first amino acid or peptide and the second amino acid or peptide. By means of this process, it is possible to synthesize a peptide at a high concentration and at a high yield, and this method is excellent for producing peptides on an industrial scale.
    Type: Grant
    Filed: January 25, 2013
    Date of Patent: April 8, 2014
    Assignee: Ajinomoto Co., Inc.
    Inventors: Shinya Furukawa, Hiroki Imai
  • Publication number: 20140086981
    Abstract: Peptides of general formula (I): R1—Wn—Xm-AA1-AA2-AA3-AA4-AA5-AA6-Yp—Zq—R2 their stereoisomers, mixtures thereof and/or their cosmetically or pharmaceutically acceptable salts, a preparation process, cosmetic or pharmaceutical compositions which contain them and their use in the treatment and/or care of conditions, disorders and/or diseases which improve or are prevented by PGC-1? modulation.
    Type: Application
    Filed: March 23, 2012
    Publication date: March 27, 2014
    Inventors: José María García Antón, Nuria Almiñana Domenech, Antonio Vicente Ferrer Montiel
  • Publication number: 20130330382
    Abstract: The invention provides an aqueous acidic formulation suitable for use as in the preparation of a pharmaceutically acceptable fluorocarbon-linked peptide formulation, which aqueous formulation comprises a first fluorocarbon-linked peptide, wherein: the peptide linked to the fluorocarbon is at least 20 amino acid residues long, comprises at least 50% hydrophobic amino acid residues and has an isoelectric point greater than or equal to 7; and the fluorocarbon-linked peptide is present in micelles.
    Type: Application
    Filed: December 30, 2011
    Publication date: December 12, 2013
    Inventors: Carlton Bradley Brown, Bertrand Victor Gilbert Georges, Jean Francois Thaburet
  • Patent number: 8569453
    Abstract: Particular compounds having a fluorene skeleton are superior in broad utility and stability, as a protecting reagent for liquid phase synthesis of amino acids and/or peptides.
    Type: Grant
    Filed: March 12, 2010
    Date of Patent: October 29, 2013
    Assignee: Ajinomoto Co., Inc.
    Inventor: Daisuke Takahashi
  • Patent number: 8546528
    Abstract: The invention is directed to peptides. Specifically, the invention is directed to peptides which bind skin and do not bind hair. Alternatively, the invention is drawn to peptides which bind hair and do not bind skin.
    Type: Grant
    Filed: August 3, 2009
    Date of Patent: October 1, 2013
    Assignee: Danisco US Inc.
    Inventors: Giselle Janssen, Christopher J. Murray, Deborah Winetzky
  • Patent number: 8546526
    Abstract: The present invention is related to new peptide antagonists of ?v?3 receptor, designed on the basis of the crystal structure of integrin ?v?3 in complex with c(RGDf[NMe]V) and the NMR structure of echistatin. These peptides are potent and selective antagonists of the ?v?3 receptor and can be used as novel anticancer drugs and/or new class of diagnostic non-invasive tracers as suitable tools for ?v?3-targeted therapy and imaging.
    Type: Grant
    Filed: October 9, 2006
    Date of Patent: October 1, 2013
    Assignee: Advanced Accelerator Applications
    Inventors: Annarita del Gatto, Laura Zaccaro, Carlo Pedone, Michele Saviano
  • Publication number: 20130245225
    Abstract: The present invention provides improved methods for the synthesis of polypeptide or peptide-linked compounds via a NCA-based polymerization reaction that produces high product yields in much less time. Such improved methods are achieved by application of a higher temperature and/or reduced pressure to the reaction such that an NCA-containing monomer melts.
    Type: Application
    Filed: May 22, 2013
    Publication date: September 19, 2013
    Inventor: Keith R. Latham
  • Publication number: 20130137853
    Abstract: Peptides may be produced by using (A) a first amino acid or peptide, which is converted into its ionic liquid form through the formation of an ionic bond, as a substance serving as both a reaction solvent and a reaction starting material; and reacting the first amino acid or peptide with (B) an ester of second amino acid or peptide, in the absence of any peptide hydrolase or any condensation agent, in the presence of water in an amount of not more than 20% by mass relative to the total mass of the reaction system to form a peptide bond between the first amino acid or peptide and the second amino acid or peptide. By means of this process, it is possible to synthesize a peptide at a high concentration and at a high yield, and this method is excellent for producing peptides on an industrial scale.
    Type: Application
    Filed: January 25, 2013
    Publication date: May 30, 2013
    Applicant: AJINOMOTO CO., INC.
    Inventor: AJINOMOTO CO., INC.
  • Patent number: 8362204
    Abstract: Described herein are methods for forming two or more dicarba bridges, as well as new compounds containing dicarba bridges.
    Type: Grant
    Filed: September 26, 2008
    Date of Patent: January 29, 2013
    Assignee: Syngene Limited
    Inventors: Andrea Robinson, Roy William Jackson, Jim Patel, Jomana Elaridi
  • Patent number: 8344103
    Abstract: A solvent system which comprises two or more single organic solvents or two or more mixed organic solvents, characterized in that the state of the solvent system can be reversibly changed, with changing temperature conditions, from one state which is a homogeneously compatibilized mixed solvent system in which the two or more single or more mixed organic solvents constituting the solvent system have been homogeneously compatibilized and mixed to the other state which is a separated solvent system made up of two or more separated phases respectively consisting mainly of the two or more single or mixed organic solvents constituting solvent system, and that when the solvent system is the homogeneously mixed solvent system, a chemical component which is soluble in only one of the single or mixed organic solvents can be evenly dissolved in the system; and a process for producing a compound with the solvent system.
    Type: Grant
    Filed: November 3, 2006
    Date of Patent: January 1, 2013
    Assignee: Japan Science and Technology Agency
    Inventors: Kazuhiro Chiba, Yusuke Kono
  • Patent number: 8314209
    Abstract: The invention herein disclosed provides for methods for the synthesis of polymers from monomers. In particular the method provides for the synthesis of polynucleotides from mononucleotides in the absence of catalytic enzymes. The method comprises providing an aqueous solution having a plurality of phospholipid molecules and monomer molecules; subjecting the aqueous solution to fluctuating temperature conditions; subjecting the aqueous solution to fluctuating cycles of drying and hydrating conditions; subjecting the aqueous solution to fluctuating [H+] conditions; the fluctuating conditions thereby allowing formation of a chemical bond between at least two monomers to create a polymer. The invention is of particular use in the fields of molecular biology, structural biology, cell biology, molecular switches, molecular circuits, and molecular computational devices, and the manufacture thereof.
    Type: Grant
    Filed: December 12, 2008
    Date of Patent: November 20, 2012
    Assignee: The Regents of the University of California
    Inventors: Sudha Rajamani, Felix Olasagasti, David W. Deamer, Seico Benner
  • Publication number: 20120253012
    Abstract: There is provided a practical method for preparing lipopeptide compounds, which method is capable of inexpensive mass production without requiring complicated operations. The lipopeptide compound of formula (3): is produced by reacting an ester compound of formula (1): with an ?-amino acid compound of formula (2): in the presence of a base and within a solvent containing a nonpolar organic solvent.
    Type: Application
    Filed: September 7, 2010
    Publication date: October 4, 2012
    Applicant: NISSAN CHEMICAL INDUSTRIES, LTD.
    Inventors: Nobuyuki Kakiuchi, Takeaki Shoji, Kazuki Hirasada, Keigo Matsumoto, Hiroki Yamaguchi
  • Patent number: 8247533
    Abstract: Disclosed are peptide structures that are stable in aqueous and non-aqueous media where a first linear peptide chain comprising alternating D,L- or L,D-amino acids having an N and C termini is joined by at least one turn region to a second linear peptide chain comprising alternating D,L- or L,D-amino acids having an N and C termini. The peptide chains can be joined at the C terminus of one of the linear peptide chains with an N terminus of the other linear peptide chain, a C terminus of one of the linear peptide chains with a C terminus of the other linear peptide chain, or an N terminus of one of the linear peptide chains with an N terminus of the other linear peptide chain.
    Type: Grant
    Filed: March 6, 2012
    Date of Patent: August 21, 2012
    Assignee: The United States of America, as represented by the Secretary of the Navy
    Inventors: John L. Kulp, III, Thomas D. Clark
  • Publication number: 20120190820
    Abstract: Provided are methods for forming a reactive S-nitroso thioacid (NTA), comprising nitrosation of a thioacid with a nitrosation reagent. Also provided are methods for: acylating a nucleophile including selective acylation with a high degree of selectivity toward amines over hydroxyls; amide or peptide bond formation; forming a dipeptide or polypeptide; and peptide coupling/ligation, comprising use of thioacid and amine starting materials, wherein the reactions are mediated by very reactive S-nitroso thioacid (NTA) intermediates enabling extremely fast reactions under mild conditions, providing for broad applications.
    Type: Application
    Filed: January 26, 2012
    Publication date: July 26, 2012
    Inventors: Ming Xian, Jia Pan
  • Patent number: 8227571
    Abstract: The present invention relates to the preparation of insulinotropic peptides that are synthesized using a solid and solution phase (“hybrid”) approach. Generally, the approach includes synthesizing three different peptide intermediate fragments using solid phase chemistry. Solution phase chemistry is then used to add additional amino acid material to the third fragment which is then coupled to the second fragment and then the first fragment in solution. Alternatively, a different second fragment is coupled to the first fragment in the solid phase. Then, solution phase chemistry is then used to add additional amino acid material to a different third fragment. Subsequently, this different third fragment is coupled to the coupled first and different second fragment in the solution phase. The use of a pseudoproline in one of the fragments eases solid phase synthesis of that fragment and also eases subsequent solution phase coupling of this fragment to the other fragments.
    Type: Grant
    Filed: December 11, 2008
    Date of Patent: July 24, 2012
    Assignee: Roche Palo Alto LLC
    Inventors: Lin Chen, Yeun-Kwei Han, Christopher R. Roberts
  • Patent number: 8217142
    Abstract: The invention relates to improved liquid phase processes for the preparation of the 21 residue protein component, (Lys-Leu4)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 ?-carbon.
    Type: Grant
    Filed: September 30, 2008
    Date of Patent: July 10, 2012
    Assignee: Ortho Pharmaceutical Corporation
    Inventors: Ahmed F. Abdel-Magid, Urs Eggmann, Cynthia Anne Maryanoff, Adrian Thaler, Frank J. Villani
  • Publication number: 20120108788
    Abstract: A reagent for organic synthesis with which a chemical reaction can be conducted in a liquid phase and unnecessary compound(s) can be easily separated at low cost from the liquid phase after completion of the reaction. The reagent for organic synthesis reversibly changes from a liquid-phase state to a solid-phase state with changes in solution composition and/or solution temperature, and is for use in organic synthesis reactions. This reagent for organic syntheses facilitates process development. With the reagent, research on and development of, e.g., medicines through, e.g., compound library synthesis, etc. can be accelerated. It can hence contribute to technical innovations in the biochemical industry and chemical industry.
    Type: Application
    Filed: January 9, 2012
    Publication date: May 3, 2012
    Applicant: JITSUBO Co., Ltd.
    Inventors: Kazuhiro Chiba, Shokaku Kim, Yusuke Kono
  • Patent number: 8163874
    Abstract: Disclosed is a method of making peptide structures that are stable in aqueous and non-aqueous media where a first linear peptide chain comprising alternating D,L- or L,D-amino acids having an N and C termini is joined by at least one turn region to a second linear peptide chain comprising alternating D,L- or L,D-amino acids having an N and C termini. The peptide chains can be joined at the C terminus of one of the linear peptide chains with an N terminus of the other linear peptide chain, a C terminus of one of the linear peptide chains with a C terminus of the other linear peptide chain, or an N terminus of one of the linear peptide chains with an N terminus of the other linear peptide chain.
    Type: Grant
    Filed: August 6, 2008
    Date of Patent: April 24, 2012
    Assignee: The United States of America, as represented by the Secretary of the Navy
    Inventors: John L Kulp, Thomas D Clark
  • Publication number: 20110275554
    Abstract: The present invention relates to prodrugs of vascular disrupting agents comprising a vascular disrupting agent (VDA) associated with a MMP proteolytic cleavage site and to the use of such prodrugs in the targeted treatment of cancer.
    Type: Application
    Filed: October 20, 2009
    Publication date: November 10, 2011
    Applicant: The University of Bradford
    Inventors: Robert Andrew Falconer, Jason Gill, Jennifer Atkinson, Paul Loadman, Michael Bibby, Laurence Patterson
  • Patent number: 8044173
    Abstract: A process comprising substitution of an acceptor molecule comprising a group —XC(O)— wherein X is O, S, or NR8, where R8 is C1-6 alkyl, C6-12 aryl or hydrogen, with a nucleophile, wherein the acceptor molecule is cyclised such that said nucleophilic substitution at —XC(O)— occurs without racemisation, is provided. This process has particular application for the production of a peptide by extension from the activated carboxy-terminus of an acyl amino acid residue without epimerisation.
    Type: Grant
    Filed: March 20, 2008
    Date of Patent: October 25, 2011
    Assignee: University of Reading
    Inventors: Laurence M. Harwood, Ran Yan
  • Patent number: 8022181
    Abstract: The present invention provides a composition and a method for cleaving a peptide from a solid support resin. Hydrochloric acid in an organic water miscible solvent is used to cleave the peptide-resin attachment. Optionally, trifluoroethanol or hexafluoroisopropanol may be added to the cleavage composition to improve results. When using the present cleavage composition, an evaporation or other step to remove carboxylic byproducts is not necessary following the cleavage reaction. After the resin is filtered out of the cleavage mixture, the peptide may be immediately precipitated with water.
    Type: Grant
    Filed: April 18, 2007
    Date of Patent: September 20, 2011
    Assignee: Mallinckrodt LLC
    Inventor: Kripa Shanker Srivastava
  • Patent number: 8021570
    Abstract: The present invention provides materials and methods that make liquid crystal phases accessible with relatively short ?-peptides in aqueous solvents.
    Type: Grant
    Filed: June 13, 2007
    Date of Patent: September 20, 2011
    Assignee: Wisconsin Alumni Research Foundation
    Inventors: Samuel H. Gellman, Nicholas L. Abbott, William C. Pomerantz
  • Publication number: 20110104063
    Abstract: A solid phase peptide synthesis method for synthesizing a peptidyl contrast agent is disclosed. In one example, the method includes synthesizing an amino-chelator loaded resin, coupling of the amino-chelator loaded resin to the C-terminus and/or backbone of a peptide, cleaving the amino-chelator-peptide from a resin, and chelating a lanthanide metal to the amino-chelator-peptide.
    Type: Application
    Filed: November 29, 2010
    Publication date: May 5, 2011
    Inventors: Mark D. Pagel, Byunghee Yoo
  • Publication number: 20110105722
    Abstract: Method for preparing a peptide or a peptide derivative which comprises it least one step in which a free amino acid or a free peptide is reacted with a urethane-protected amino acid N-carboxyanhydride (UNCA) solution.
    Type: Application
    Filed: March 6, 2009
    Publication date: May 5, 2011
    Applicant: SOLVAY (SOCIETE ANONYME)
    Inventors: Roland Callens, Laurent Jeannin
  • Patent number: 7919580
    Abstract: A polysaccharide-protein binding model of SBD, and a fibril-forming 14-residue peptide consisting of X1NNNX2X3NYQX4X5X6X7X8, wherein the X1 and X8 mean a pair of opposite charged amino acid residues, and the X2, X3, X4, X5, X6, or X7 means an amino acid residue is described. A mixture for diminising a polysaccharide, comprising at least two starch binding domains (SBDs) and a polysaccharide in a helix form is also presented. A method of providing an oligosaccharide, and a method of producing an amyloid-like fibril and use thereof are further described.
    Type: Grant
    Filed: January 23, 2009
    Date of Patent: April 5, 2011
    Assignee: National Tsing Hua University
    Inventors: Margaret Dah-Tsyr Chang, Yuh-Ju Sun, Ping-Chiang Lyu, Shu-Chuan Lin, Wei-I Chou
  • Publication number: 20100292439
    Abstract: A subject of the invention is the use of a salt with a dedicated task of formula (I): A+-L-R—OY, X? as soluble support for peptide synthesis, in which: X? represents a functional or non-functional anion, Y represents either a hydrogen atom, or a —COOR1 group, R1 representing in particular an alkyl group comprising 1 to 20 carbon atoms, A+ represents a cationic entity, L represents an arm, in particular an alkyl group of 3 to 20 carbon atoms, R represents in particular a group of formula —C(Ra)(Rb)—, Ra and Rb representing independently of one another in particular a hydrogen or an alkyl group, comprising 1 to 20 carbon atoms.
    Type: Application
    Filed: July 5, 2006
    Publication date: November 18, 2010
    Applicants: CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE`, UNIVERSITE DE RENNES
    Inventors: Michel Vaultier, Céline Roche, Saïd Gmouh, Alain Commercon
  • Patent number: 7820162
    Abstract: The invention provides methods of chemically synthesizing chimeric proteins comprising at least a portion of an immunoglobulin constant region and a biologically active molecule.
    Type: Grant
    Filed: April 9, 2008
    Date of Patent: October 26, 2010
    Assignee: Syntonix Pharmaceuticals, Inc.
    Inventors: Adam R. Mezo, Robert T. Peters
  • Publication number: 20100184660
    Abstract: The present invention relates to novel bio-active peptide hormone, process for the production of the same, and use of the same. The present invention identified novel bioactive peptide precursor and salts thereof which can be used as drugs, for example therapeutic polypeptides, ligands to discover relevant targets (e.g. GPCRs) or targets for drug intervention.
    Type: Application
    Filed: December 12, 2007
    Publication date: July 22, 2010
    Applicant: SANOFI-AVENTIS
    Inventors: Eva Jung, Werner Dittrich, Sabine Scheidler
  • Publication number: 20100184232
    Abstract: An oligo peptide synthesis apparatus comprises a stationary apparatus part, which is stationary in relation to the frame and a movable apparatus part. The movable apparatus part comprises an oligo peptide synthesis reaction holder, which comprises a number of receptors for receiving a corresponding number of vessels and the receptors are located on a circle. The movable apparatus part comprises a revolveable holder, which has a disengageable coupling for connecting the revolveable holder to the oligo peptide synthesis reaction holder.
    Type: Application
    Filed: May 9, 2008
    Publication date: July 22, 2010
    Inventor: Peter Jepsen
  • Publication number: 20100167981
    Abstract: Methods are provided for the utilization of bacterial cell-free extracts in the synthesis of high yields of virus like particles with encapsidated cargo.
    Type: Application
    Filed: November 18, 2009
    Publication date: July 1, 2010
    Inventors: Bradley C. Bundy, James R. Swartz, Wei Chan
  • Patent number: 7718598
    Abstract: This invention relates to methods for preparing cyclic peptides and peptidomimetic compounds in solution and bound to solid supports, and to cyclic peptide or peptidomimetic libraries for use in drug screening programmes. In particular, the invention relates to a generic strategy for synthesis of cyclic peptides or peptidomimetics that enables the efficient synthesis under mild conditions of a wide variety of desired compounds. Two approaches were evaluated for their improvements in solution and solid phase synthesis of small cyclic peptides: positioning reversible N-amide substituents in the sequence; and applying native ligation chemistry in an intramolecular sense. Systematic investigation of the effects of preorganizing peptides prior to cyclisation by using peptide cyclisation auxiliaries, and developing new linkers and peptide cyclisation auxiliaries to aid cyclic peptide synthesis gives surprising improvements in both yields and purity of products compared to the prior art methods.
    Type: Grant
    Filed: September 24, 1999
    Date of Patent: May 18, 2010
    Assignee: The University of Queensland
    Inventors: Mark Leslie Smythe, Wim Denis Frans Meutermans
  • Publication number: 20100093001
    Abstract: The present invention relates to the field of amyloid disorders, more particularly to the field of diseases where protein misfolding leads to the generation of insoluble amyloid fibers in tissues and organs. The invention provides methods for the production of soluble, toxic amyloid oligomers. The invention further provides assays using the amyloid oligomers to screen for molecules that interfere with the toxicity of the oligomers.
    Type: Application
    Filed: September 6, 2007
    Publication date: April 15, 2010
    Inventors: Frederic Rousseau, Joost Schymkowitz, Ivo da Rocha Martins, Bart De Strooper
  • Publication number: 20100009904
    Abstract: Novel exendins with modifications at one or more of following positions: 2, 14, 27 or 28 and polyethylene glycol derivatives thereof are provided. These compounds are useful in treating type 2 diabetes as GLP-1 receptor agonists.
    Type: Application
    Filed: January 10, 2006
    Publication date: January 14, 2010
    Applicant: Wuxi Grandchamp Pharmaceutical Technology Co., Ltd
    Inventors: Aifeng Lv, Changan Sun, Yali Wang
  • Publication number: 20100009427
    Abstract: Fluorescent metal nanoclusters were prepared.
    Type: Application
    Filed: April 10, 2007
    Publication date: January 14, 2010
    Applicant: Los Alamos National Security, LLC
    Inventors: Jennifer S. Martinez, R. Brian Dyer, Dung M. Vu, Yuping Bao, Chang Zhong
  • Publication number: 20090292108
    Abstract: The present invention relates to the preparation of insulinotropic peptides that are synthesized using a solid and solution phase (“hybrid”) approach. Generally, the approach includes synthesizing three different peptide intermediate fragments using solid phase chemistry. Solution phase chemistry is then used to add additional amino acid material to the third fragment which is then coupled to the second fragment and then the first fragment in solution. Alternatively, a different second fragment is coupled to the first fragment in the solid phase. Then, solution phase chemistry is then used to add additional amino acid material to a different third fragment. Subsequently, this different third fragment is coupled to the coupled first and different second fragment in the solution phase. The use of a pseudoproline in one of the fragments eases solid phase synthesis of that fragment and also eases subsequent solution phase coupling of this fragment to the other fragments.
    Type: Application
    Filed: December 11, 2008
    Publication date: November 26, 2009
    Inventors: Lin Chen, Yeun-Kwei Han, Christopher R. Roberts
  • Publication number: 20090280170
    Abstract: The present invention provides compositions of GnRH related compounds that are suitable for oral administration, injectable administration and other forms of administration wherein the gelling characteristics of the composition are a factor. The compositions of the present invention comprise a therapeutically effective amount of one or more GnRH related compound, and a sufficient amount of at least one anti-gelling agents to reduce the gelation of the GnRH related compound. The present invention also provides processes for preparation of a composition of one or more GnRH related compound, wherein the process comprises mixing the GnRH related compound with one or more anti-gelling agents, wherein the anti-gelling agent comprises a medium chain fatty acid salt, or an ester, an ether, or a derivative of a medium chain fatty acid and has a carbon chain length of from about 4 to about 20 carbon atoms or is a surface active agent.
    Type: Application
    Filed: May 7, 2009
    Publication date: November 12, 2009
    Inventors: Amanda Lee, Bozena Adamczyk, David C. Coughlan, Edel O'Toole, Thomas W. Leonard
  • Publication number: 20090264621
    Abstract: The invention herein disclosed provides for methods for the synthesis of polymers from monomers. In particular the method provides for the synthesis of polynucleotides from mononucleotides in the absence of catalytic enzymes. The invention is of particular use in the fields of molecular biology, structural biology, cell biology, molecular switches, molecular circuits, and molecular computational devices, and the manufacture thereof.
    Type: Application
    Filed: December 12, 2008
    Publication date: October 22, 2009
    Inventors: Sudha Rajamani, Felix Olasagasti, David W. Deamer, Seico Benner
  • Patent number: 7589170
    Abstract: This invention relates to methods for preparing cyclic peptides and peptidomimetic compounds in solution and bound to solid supports, and to cyclic peptide or peptidomimetic libraries for use in drug screening programs. In particular, the invention relates to a generic strategy for synthesis of cyclic peptides or peptidomimetics that enables the efficient synthesis under mild conditions of a wide variety of desired compounds. Two approaches were evaluated for their improvements in solution and solid phase synthesis of small cyclic peptides: positioning reversible N-amide substituents in the sequence; and applying native ligation chemistry in an intramolecular sense. Systematic investigation of the effects of preorganising peptides prior to cyclisation by using peptide cyclisation auxiliaries, and developing new linkers and peptide cyclisation auxiliaries to aid cyclic peptide synthesis gives surprising improvements in both yields and purity of products compared to the prior art methods.
    Type: Grant
    Filed: September 24, 1999
    Date of Patent: September 15, 2009
    Assignee: The University of Queensland
    Inventors: Mark Leslie Smythe, Wim Denis Frans Meutermans, Gregory Thomas Bourne, Ross Peter McGeary
  • Patent number: 7576059
    Abstract: A pharmacologically active peptide hormone derivative in which the parent peptide hormone has been modified by introducing either a lipophilic substituent, W, in the N-terminal amino acid or a lipophilic substituent, Z, in the C-terminal amino acid of the parent peptide hormone or an analogue thereof, said lipophilic substituent having from 8 to 40 carbon atoms, has a protracted profile of action.
    Type: Grant
    Filed: January 30, 2001
    Date of Patent: August 18, 2009
    Assignee: Novo Nordisk A/S
    Inventors: Ib Jonassen, Svend Havelund, Per Hertz Hansen, Peter Kurtzhals, John B. Halstrøm
  • Patent number: 7566697
    Abstract: The present invention provides methods of assembling oligopeptides or polypeptides in a native chemical ligation reaction that eliminates the formation of unwanted side products resulting from the presence of an unprotected acidic C-terminal oligopeptide thioester. An important aspect of the present invention is providing side chain protected acidic C-terminal oligopeptide thioesters. The present invention is useful in methods for chemical synthesis of oligopeptides, polypeptides and proteins and improves the efficiency of native chemical ligation reactions, particularly where aspartyl or glutamyl peptide fragments are used to assemble an oligopeptide, polypeptide or protein product.
    Type: Grant
    Filed: June 9, 2003
    Date of Patent: July 28, 2009
    Assignee: Amylin Pharmaceuticals, Inc.
    Inventors: Paolo Botti, Matteo Villain, Sonia Manganiello, Hubert Gaertner
  • Publication number: 20090186369
    Abstract: The present invention relates to a polysaccharide-protein binding model of SBD, and a fibril-forming 14-residue peptide consisting of X1NNNX2X3NYQX4X5X6X7X8, wherein the X1 and X8 mean a pair of opposite charged amino acid residues, and the X2, X3, X4, X5, X6, or X7 means an amino acid residue. The present invention also relates to a mixture for diminising a polysaccharide, comprising at least two starch binding domains (SBDs) and a polysaccharide in a helix form. The present invention further relates to a method of providing an oligosaccharide, and a method of producing an amyloid-like fibril and use thereof.
    Type: Application
    Filed: January 23, 2009
    Publication date: July 23, 2009
    Applicant: NATIONAL TSING HUA UNIVERSITY
    Inventors: Margaret Dah-Tsyr Chang, Yuh-Ju Sun, Ping-Chiang Lyu, Shu-Chuan Lin, Wei-I Chou
  • Publication number: 20090149628
    Abstract: The present invention relates to the preparation of insulinotropic peptides that are synthesized using a solid and solution phase (“hybrid”) approach. Generally, the approach includes synthesizing three different peptide intermediate fragments using solid phase chemistry. Solution phase chemistry is then used to add additional amino acid material to one of the fragments. The fragments are then coupled together in the solution phase. The use of a pseudoproline in one of the fragments eases solid phase synthesis of that fragment and also eases subsequent solution phase coupling of this fragment to other fragments. The present invention is very useful for forming insulinotropic peptides such as Exenatide(1-39) and its natural and non-natural counterparts.
    Type: Application
    Filed: October 24, 2008
    Publication date: June 11, 2009
    Inventors: Barry Thomas King, Paul Adam Bury, Richard A. Gabel, John Edward Crider, Robert Thad Carr, II, Bradley S. DeHoff
  • Publication number: 20090069538
    Abstract: The present invention is related to a method of producing a peptide, characterized in contacting a reaction mixture with a base after a condensation reaction to hydrolyze while a basic condition is maintained until a ratio of a remaining unreacted active ester of an acid component is decreased to 1% or less in a liquid phase peptide synthesis method. According to the invention, a target peptide of high purity can be simply and efficiently produced by a continuous liquid phase synthesis method. Further, the present invention is related to a method of producing a peptide, characterized in using an amide-type solvent immiscible with water in a liquid phase peptide synthesis method. According to the invention, various peptides can be produced by the liquid phase synthesis method without being restricted by the amino acid sequence of the target peptide.
    Type: Application
    Filed: July 31, 2006
    Publication date: March 12, 2009
    Inventors: Hiroshi Murao, Ken-ichiro Morio, Masaru Mitsuda