DOE Patents title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: Targeted polypeptide degradation

Abstract

This invention pertains to compositions, methods, cells and organisms useful for selectively localizing polypeptides to the proteasome for degradation. Therapeutic methods and pharmaceutical compositions for treating disorders associated with the expression and/or activity of a polypeptide by targeting these polypeptides for degradation, as well as methods for targeting therapeutic polypeptides for degradation and/or activating therapeutic polypeptides by degradation are provided. The invention provides methods for identifying compounds that mediate proteasome localization and/or polypeptide degradation. The invention also provides research tools for the study of protein function.

Inventors:
 [1];  [1]
  1. Brookline, MA
Issue Date:
Research Org.:
Harvard University
Sponsoring Org.:
USDOE
OSTI Identifier:
983006
Patent Number(s):
7371539
Application Number:
11/003,103
Assignee:
President and Fellows of Harvard College (Cambridge, MA)
Patent Classifications (CPCs):
C - CHEMISTRY C07 - ORGANIC CHEMISTRY C07K - PEPTIDES
C - CHEMISTRY C12 - BIOCHEMISTRY C12N - MICROORGANISMS OR ENZYMES
DOE Contract Number:  
FG02-87ER60565
Resource Type:
Patent
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES

Citation Formats

Church, George M, and Janse, Daniel M. Targeted polypeptide degradation. United States: N. p., 2008. Web.
Church, George M, & Janse, Daniel M. Targeted polypeptide degradation. United States.
Church, George M, and Janse, Daniel M. Tue . "Targeted polypeptide degradation". United States. https://www.osti.gov/servlets/purl/983006.
@article{osti_983006,
title = {Targeted polypeptide degradation},
author = {Church, George M and Janse, Daniel M},
abstractNote = {This invention pertains to compositions, methods, cells and organisms useful for selectively localizing polypeptides to the proteasome for degradation. Therapeutic methods and pharmaceutical compositions for treating disorders associated with the expression and/or activity of a polypeptide by targeting these polypeptides for degradation, as well as methods for targeting therapeutic polypeptides for degradation and/or activating therapeutic polypeptides by degradation are provided. The invention provides methods for identifying compounds that mediate proteasome localization and/or polypeptide degradation. The invention also provides research tools for the study of protein function.},
doi = {},
journal = {},
number = ,
volume = ,
place = {United States},
year = {Tue May 13 00:00:00 EDT 2008},
month = {Tue May 13 00:00:00 EDT 2008}
}

Works referenced in this record:

The Ubiquitin System
journal, June 1998


Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans
journal, February 1998


Targeted mutation of the DNA methyltransferase gene results in embryonic lethality
journal, June 1992


Construction of a set of convenientsaccharomyces cerevisiae strains that are isogenic to S288C
journal, January 1995


Forced engagement of a RNA/protein complex by a chemical inducer of dimerization to modulate gene expression
journal, February 2002


A gated channel into the proteasome core particle
journal, November 2000


Inducible gene expression and protein translocation using nontoxic ligands identified by a mammalian three-hybrid screen
journal, July 1997


Development of Protacs to Target Cancer-promoting Proteins for Ubiquitination and Degradation
journal, October 2003


Applications of Combinatorial Technologies to Drug Discovery. 1. Background and Peptide Combinatorial Libraries
journal, April 1994


Deadly encounter: ubiquitin meets apoptosis
journal, February 2002


Controlling signal transduction with synthetic ligands
journal, November 1993


Protacs: Chimeric molecules that target proteins to the Skp1-Cullin-F box complex for ubiquitination and degradation
journal, July 2001


Ca 2+ -free Calmodulin and Calmodulin Damaged by in Vitro Aging Are Selectively Degraded by 26 S Proteasomes without Ubiquitination
journal, April 2000


Discovery of Nanomolar Ligands for 7-Transmembrane G-Protein-Coupled Receptors from a Diverse N-(Substituted)glycine Peptoid Library
journal, August 1994


Crystal structure of heat shock locus V (HslV) from Escherichia coli
journal, June 1997


A Novel Procedure for the Synthesis of Libraries Containing Small Organic Molecules
journal, November 1994


Ubiquitinylation is not an absolute requirement for degradation of c- Jun protein by the 26 S proteasome
journal, May 1995


Viable offspring derived from fetal and adult mammalian cells
journal, February 1997


Recombinase-mediated gene activation and site-specific integration in mammalian cells
journal, March 1991


The Proteasome
journal, June 1999


Modifying the mammalian genome by gene targeting
journal, December 1991


A humanized system for pharmacologic control of gene expression
journal, September 1996


ATP-Dependent Proteases Degrade Their Substrates by Processively Unraveling Them from the Degradation Signal
journal, March 2001


HeterologousHIS3 Marker and GFP Reporter Modules for PCR-Targeting inSaccharomyces cerevisiae
journal, September 1997


Activation of the Raf-1 kinase cascade by coumermycin-induced dimerization
journal, September 1996


An Unnatural Biopolymer
journal, September 1993


Searching for peptide ligands with an epitope library
journal, July 1990


In vivo half-life of a protein is a function of its amino-terminal residue
journal, October 1986


Dexamethasone−Methotrexate:  An Efficient Chemical Inducer of Protein Dimerization In Vivo
journal, May 2000


"Diversomers": an approach to nonpeptide, nonoligomeric chemical diversity.
journal, August 1993


A Solution-Phase Screening Procedure for the Isolation of Active Compounds from a Library of Molecules
journal, November 1994


Targeted modification and transportation of cellular proteins
journal, December 2000


Screening for receptor ligands using large libraries of peptides linked to the C terminus of the lac repressor.
journal, March 1992


Substrate access and processing by the 20S proteasome core particle
journal, May 2003


α-Synuclein metabolism and aggregation is linked to ubiquitin-independent degradation by the proteasome
journal, November 2001


A proteasomal ATPase subunit recognizes the polyubiquitin degradation signal
journal, April 2002


The structures of HslU and the ATP-dependent protease HslU–HslV
journal, February 2000


Recognition of Misfolding Proteins by PA700, the Regulatory Subcomplex of the 26 S Proteasome
journal, February 2000


A new efficient gene disruption cassette for repeated use in budding yeast
journal, July 1996


Targets for cell cycle arrest by the immunosuppressant rapamycin in yeast
journal, August 1991


Selection of antibody ligands from a large library of oligopeptides expressed on a multivalent exposition vector
journal, November 1991


PAN, the proteasome-activating nucleotidase from archaebacteria, is a protein-unfolding molecular chaperone
journal, October 2000


Regulation of cellular polyamines by antizyme
journal, March 2001


Peptides on phage: a vast library of peptides for identifying ligands
journal, August 1990


TOR Mutations Confer Rapamycin Resistance by Preventing Interaction with FKBP12-Rapamycin
journal, November 1995


Structure of 20S proteasome from yeast at 2.4Å resolution
journal, April 1997


Controlling protein association and subcellular localization with a synthetic ligand that induces heterodimerization of proteins.
journal, May 1996


Chemically induced dimerization of dihydrofolate reductase by a homobifunctional dimer of methotrexate
journal, May 2000


Structural basis for the activation of 20S proteasomes by 11S regulators
journal, November 2000


Recursive deconvolution of combinatorial chemical libraries.
journal, November 1994


Protein unfolding — an important process in vivo?
journal, February 2003


Multiplexed biochemical assays with biological chips
journal, August 1993


Targeted oncogene activation by site-specific recombination in transgenic mice.
journal, July 1992


Site-directed mutagenesis by gene targeting in mouse embryo-derived stem cells
journal, November 1987


Random peptide libraries: a source of specific protein binding molecules
journal, July 1990


Dimeric ligands define a role for transcriptional activation domains in reinitiation
journal, August 1996


A new type of synthetic peptide library for identifying ligand-binding activity
journal, November 1991


Role of the proteasome and NF- B in streptococcal cell wall-induced polyarthritis
journal, December 1998


Proteasomal degradation of tau protein: Tau and the proteasome
journal, September 2002


The base of the proteasome regulatory particle exhibits chaperone-like activity
journal, July 1999