Abstract: A method for the structure-based identification and selection of inhibitors of processivity factor binding to protein is disclosed herein. Characterization of the protein/processivity factor interface is given. Methods for the structure-based inhibition of processivity factor binding to protein are also given. One embodiment includes a class of peptidomimetics that mimic helical portions of proteins. In addition, methods of treatment of various diseases are given, using the inhibitors of the invention.
Type:
Grant
Filed:
May 12, 2000
Date of Patent:
June 17, 2008
Assignee:
President and Fellows of Harvard College
Inventors:
Donald Coen, James Hogle, Carl Elkin, Harmon J. Zuccola, Kristie Grove Bridges, Scott Lokey
Abstract: The sequences of cDNAs encoding secreted proteins are disclosed. The cDNAs can be used to express secreted proteins or fragments thereof or to obtain antibodies capable of specifically binding to the secreted proteins. The cDNAs may also be used in diagnostic, forensic, gene therapy, and chromosome mapping procedures. The cDNAs may also be used to design expression vectors and secretion vectors.
Abstract: The present invention relates to a data storage medium encoded with the corresponding structure coordinates of molecules and molecular complexes which comprise the active site-binding pockets of JNK3. A computer comprising such data storage material is capable of displaying such molecules and molecular complexes, or their structural homologues, as a graphical three-dimensional representation on a computer screen. This invention also relates to methods of using the structure coordinates to solve the structure of homologous proteins or protein complexes. In addition, this invention relates to methods of using the structure coordinates to screen and design compounds, including inhibitory compounds, that bind to JNK3 or homologues thereof. This invention also relates to molecules and molecular complexes which comprise the active site binding pockets of JNK3 or close structural homologues of the active site binding pockets.
Type:
Grant
Filed:
November 3, 2000
Date of Patent:
June 3, 2008
Assignee:
Vertex Pharmaceuticals Incorporated
Inventors:
Xiaoling Xie, Yong Gu, William Markland, Michael S Su, Paul R Caron, Edward Fox, Keith P Wilson
Abstract: A novel class of compounds, known as peptide nucleic acids, bind complementary ssDNA and RNA strands more strongly than a corresponding DNA. The peptide nucleic acids generally comprise ligands such as naturally occurring DNA bases attached to a peptide backbone through a suitable linker.
Type:
Grant
Filed:
May 23, 2002
Date of Patent:
May 27, 2008
Inventors:
Ole Buchardt, Michael Egholm, Peter Eigil Nielsen, Rolf Henrik Berg
Abstract: A prediction method for predicting the effect of an amino acid modification on the rate of aggregation (solubility) of a reference polypeptide comprising: calculating the difference in hydrophobicity (?Hydr) between the reference polypeptide and a modified polypeptide, calculating the difference in ?-sheet propensity (??Gcoil-?+??G?-coil) between the reference polypeptide and modified polypeptide, calculating the difference in charge (? Charge) between the reference polypeptide and modified polypeptide, and calculating: [x*?Hydr]+[y*(??Gcoil-?+??G?-coil)]?[z*? Charge], wherein x, y and z are scaling factors.
Type:
Grant
Filed:
July 19, 2005
Date of Patent:
May 27, 2008
Assignee:
Cambridge University Technical Services Ltd.
Inventors:
Christopher Dobson, Fabrizio Chiti, Jesus Zurdo
Abstract: The invention relates to the use of protein design automation (PDA) to generate computationally prescreened secondary libraries of proteins, and to methods and compositions utilizing the libraries.
Type:
Grant
Filed:
September 18, 2003
Date of Patent:
May 27, 2008
Assignee:
Xencor
Inventors:
Bassil I. Dahiyat, Robert J. Hayes, Jöerg Bentzien, Klaus M. Fiebig
Abstract: The present invention is directed to peptide analogues of glucagon-like peptide-1, the pharmaceutically-acceptable salts thereof, to methods of using such analogues to treat mammals and to pharmaceutical compositions useful therefor comprising said analogues.
Type:
Grant
Filed:
December 7, 1999
Date of Patent:
May 6, 2008
Assignees:
Societe de Conseils de Recherches et d'Applications Scientifiques, SAS, The Administrators of the Tulane Educational Fund
Abstract: The present invention presents a new approach to rapidly obtaining precise high-dimensional NMR spectral information, named “GFT NMR spectroscopy”, which is based on the phase sensitive joint sampling of the indirect dimensions spanning a subspace of a conventional NMR experiment. The phase-sensitive joint sampling of several indirect dimensions of a high-dimensional NMR experiment leads to largely reduced minimum measurement times when compared to FT NMR. This allows one to avoid the “sampling limited” data collection regime. Concomitantly, the analysis of the resulting checmical shift multiplets, which are edited by the G-matrix transformation, yields increased precision for the measurement of the chemical shifts. Additionally, methods of conducting specific GFT NMR experiments as well as methods of conducting a combination of GFT NMR experiments for rapidly obtaining precise chemical shift assignment and determining the structure of proteins or other molecules are disclosed.
Type:
Grant
Filed:
October 26, 2004
Date of Patent:
April 29, 2008
Assignee:
The Research Foundation of State University of New York
Inventors:
Thomas A. Szyperski, Seho Kim, Hanudatta S. Atreya
Abstract: Method for determining the titer (concentration) of biological agents, such as viral vectors for gene transfer, in real time, in living target cells and uses thereof in the field of gene therapy and diagnosis.
Abstract: Generally, the present invention provides a number of procedures to spatially profile proteins by using hydrophobic moments. In all procedures, a hydrophobicity distribution of a protein is shifted and normalized. In one procedure, a shape or profile of a curve of a second-order moment of hydrophobicity is determined. A second procedure involves determining one or more ratios, such as the ratio of a distance at which the second order moment of hydrophobicity vanishes to the distance at which a zero-order moment of hydrophobicity vanishes. The distance at which a peak occurs in a profile of the zero- or second-order moment of hydrophobicity can also be used for comparison. For many of these procedures, a surface or profiling contour can be chosen and used to accumulate hydrophobicities and to determine the moments. These procedures can be combined to provide a good mathematical determination of whether a protein belongs to a particular class of proteins.
Type:
Grant
Filed:
March 27, 2001
Date of Patent:
March 11, 2008
Assignee:
International Business Machines Corporation
Abstract: The invention relates to novel semaphorins which are distinguished by a particular domain structure and derivatives thereof, nucleic acids (DNA, RNA, cDNA) which code for these semaphorins, and derivatives thereof, and the use thereof. The present invention relates to semaphorins which have a novel, as yet undisclosed and unexpected domain structure and which possess a biochemical function in the immune system (immunomodulating semaphorins). The novel semaphorins are referred to as type L semaphorins (SemaL). They comprise an N-terminal signal peptide, a characteristic Sema domain and, in the C-terminal region of the protein, an immunoglobulin-like domain and a hydrophobic domain which represents a potential transmembrane domain.
Abstract: The invention relates to the use of protein design automation (P DA) to generate computationally prescreened secondary libraries of proteins, and to methods and compositions utilizing the libraries.
Type:
Grant
Filed:
August 10, 2001
Date of Patent:
January 1, 2008
Assignee:
Xencor
Inventors:
Bassil I. Dahiyat, Jörg Bentzien, Klaus M. Fiebig, Robert J. Hayes
Abstract: An immunogenic detoxified protein is provided which comprises the amino acid sequence of subunit A of an E. coli heat labile toxin (LT-A) or a fragment thereof in which at least amino acid Ala-72 of the A subunits mutated, preferably by substitution with Arg. The toxoid is useful as vaccine against an enterotoxigenic strain of E. coli and is produced by recombinant DNA means by site-directed mutagenesis. It is also an effective adjuvant.
Abstract: Cyclic homodetic peptides having a repeating D-L-chirality motif are shown to have a stable disk conformation with the amino acid side chains extending radially outward and the carbonyl and amino groups extending axially upward or downward. Such cyclic peptides can be employed as subunits in the assembly of molecular tubes. Cyclic peptides having a repeating D-L-chirality motif and lacking mutually repulsive side-chains are shown to stack atop one another in an anti-parallel fashion and are shown to be held together by the formation of ?-sheet hydrogen bonding. The stacked cyclic peptides form a molecular tube having a central channel. The diameter of the channel is determined by the size cyclic peptide. If the cyclic peptide includes ionizable amino acid residues, e.g. glutamic acid or lysine, assembly and disassembly of the molecular tubes can be controlled by varying the pH. If the cyclic peptide includes hydrophobic amino acid residues, the molecular tube will insert into a lipid membrane.
Abstract: The invention relates to compounds of formula (I) or (II), which are of interest especially for inhibition of polymerization of amyloid ? peptide, as model substances for synthesis of amyloid ? peptide-ligands, as tools for the identification of other organic compounds with similar functional properties and/or as ligands for detection of amyloid deposits using e.g., positron emission tomography (PET).
Type:
Grant
Filed:
November 26, 2003
Date of Patent:
October 30, 2007
Assignee:
Neurochem (International) Limited
Inventors:
Christer Nordstedt, Jan Näslund, Johan Thyberg, Lars O. Tjernberg, Lars Terenius
Abstract: Disclosed is a method of visualizing large-scale protein interaction data, comprising the steps of (1) producing an initial layout by placing all nodes of protein interaction data on the surface of a sphere by increasing horizontal and vertical angles of polar coordinates; and (2) yielding a graph by iterating a process moving each node of the initial layout to an equilibrium position considering global spring forces between non-adjacent nodes as well as local spring forces between adjacent nodes on a predetermined number of times, by which large-scale protein interaction data is effectively visualized in a three-dimensional space. The method for visualization of the present invention, which is much faster than the conventional algorithms, can be used for interactive analysis, as well as provide an integrated system capable of directly visualizing query results from a protein-protein interaction database.
Type:
Grant
Filed:
November 7, 2002
Date of Patent:
October 9, 2007
Assignee:
Inha University Foundation, Inha University
Abstract: Methods, compositions, and devices for stimulating the number and/or differentiation of hematopoietic cells in vitro are provided. The methods involve contacting the hematopoietic cells with an inhibitor of dipeptidyl peptidase (DPIV) in the absence of exogenously provided cytokines.
Abstract: The present invention provides peptides and peptide analogues that mimic the structural and pharmacological properties of human ApoA-I. The peptides and peptide analogues are useful to treat a variety of disorders associated with dyslipidemia.
Abstract: The current invention provides methods of improving folding of polypeptides using a poorly folding domain as a component of a fusion protein comprising the poorly folding domain and a polypeptide of interest to be improved. The invention also provides novel green fluorescent proteins (GFPs) and red fluorescent proteins that have enhanced folding properties.