Data processing: structural design – modeling – simulation – and em – Simulating nonelectrical device or system – Biological or biochemical
Reexamination Certificate
2005-11-15
2005-11-15
Moran, Marjorie (Department: 1631)
Data processing: structural design, modeling, simulation, and em
Simulating nonelectrical device or system
Biological or biochemical
C703S002000, C702S027000, C435S007100
Reexamination Certificate
active
06965850
ABSTRACT:
The present invention relates to methods and agonist/antagonist compounds for modulating nuclear receptor coactivator binding. The invention includes a method for identifying residues comprising a coactivator binding site for a nuclear receptor of interest. Also included is a method of identifying agonists and/or antagonists that bind to a coactivator binding site of a nuclear receptor of interest. Agonists and antagonists of coactivator binding to nuclear receptors also are provided. The invention is exemplified by identification and manipulation of the coactivator binding site of the thyroid receptor (TR), and compounds that bind to this sites. The methods can be applied to other nuclear receptors including RAR, RXR, PPAR, VDR, ER, GR, PR, MR, and AR.
REFERENCES:
patent: 5331573 (1994-07-01), Balaji et al.
patent: 5500807 (1996-03-01), Lavin et al.
patent: 6266622 (2001-07-01), Scanlan et al.
patent: WO 97/21993 (1997-06-01), None
patent: WO 97/35195 (1997-09-01), None
patent: WO 99/27365 (1999-06-01), None
patent: WO 99/50658 (1999-10-01), None
patent: WO 99/60014 (1999-11-01), None
Accession P10828 GenBank Jun. 15, 2002.
Accession CAA68539 GenBank Sep. 25, 1995.
Ribeiro et al., “Mechanisms of Thyroid Hormone Action: Insights from X-ray Crystallographic and Functional Studies”, Recent Progress in Hormone Research vol. 53 1998, pp. 351-395.
Darimont et al. Structure and specificity of nuclear receptor-coactivator interactions. Genes & Development, vol. 12, pp. 3343-3356,.Nov. 1, 1998.
Adams et al., “Cross-validated maximum likelihood enhances crystallographic simulated annealing refinement,” Proc. Natl. Acad. Sci., vol. 94, pp. 5018-5023, 1997.
Apriletti et al., “Expression of the Rat α1 Thyroid Hormone Receptor Ligand Binding Domain inEscheria coliand the Use of a Ligand-induced Comformation Change as a Method for its purification to Homogeneity,” Protein Expr. Pruif., vol. 6, pp. 363-370, 1995.
Berry et al., “Role of the two activating domains of the oestrogen receptor in the cell-type and promoter-context dependent agonistic activity of the anti-oestrogen 4-hydroyamoxifen,” EMBO J., vol. 9, No. 9, pp. 2811-2818, 1990.
Bourguet et al., “Crystal Structure of the Ligand-binding domain of the Human Nuclear Receptor RXR-α,” Nature, vol. 375, pp. 377-382, 1995.
Brzozowski et al., “Molecular Basis of agonism and Antagonism in the oestrogen receptor,” Nature, vol. 389, pp.753-758, 1997.
Chang et al., “A Thyroid Hormone Receptor Coactivator Negatively Regulated by the Retinoblastoma Protein,” Proc. Natl. Acad. Sci. USA, vol. 94, pp. 9040-9045, 1997.
Cohen et al., “Molecular Modeling Software and Methods for Medicinal Chemistry,” J. Med. Chem., vol. 33, No. 3, pp. 883-894, 1990.
Collingwood et al., “A Natural Transactivation Mutation in the Thyroid Hormone β Receptor: Impaired Interaction wiht Putative Transcriptional Mediators,” Proc. Natl. Acad. Sci. USA, vol. 94, pp. 248-253, 1997.
Desjarlais et al., “Using Shape Complementarily as an Initial Screen in Designing Ligands for a Receptor Binding Site of Known Three-Dimensional Structure,” J. Med. Chem., vol. 31, pp. 722-729, 1988.
Ding et al., “Nuclear Receptor-Binding Sites of Coactivators Glucocorticoid Receptor Interacting Protein 1 (GRIP1) and Steroid Receptor Coactivator 1 (SRC-1): Multiple Motifs with Different Binding Specificities,” Molecular Endocrinology, vol. 12, No. 2, pp. 301-313, 1998.
Eng et al., “Probing the Structure and Function of the Estrogen Receptor Ligand Binding Domain by Analysis of Mutants with Altered Transactivation Characteristics,” Molecular and Cellular Biology, vol. 17, No. 8, pp. 4644-4653, 1997.
Farmer, “Drug Design,” Ariens, E.J., ed., vol. 10, pp. 119-143, Academic Press, NY, 1980.
Furey et al., “‘Phases’—A Program Package for the Processing and Analysis of Diffraction Data From Macromolecules,” Am. Crust. Assoc. Mtg. Abstr., PA 33, vol. 18, pp. 73, 1990.
Glass et al., “Nuclear Receptor Coactivators,” Curr. Opin. Cell Bio., vol. 9, pp. 222-232, 1997.
Greene et al., “Monoclonal Antibodies to Human Estrogen Receptor,” Proc. Natl. Acad. Sci. USA, vol. 77, No. 9, pp. 5115-5119, 1980.
Greene et al., “Purification of T47D Human Progesterone Receptor and Immunochemical Characterization with Monoclonal Antibodies,” Molecular Endocrinology, vol. 2, No. 8, pp. 714-726, 1988.
Hegy et al., “Carboxymethylation of the Human Estrogen Receptor Ligand-Binding Domain-Estradiol Complex: HPLC/ESMS Peptide Mapping Shows That Cysteine 447 Does Not React With Iodoacetic Acid,” Steroids, vol. 61:367-373 (1996).
Heery et al., “A Signature Motif in Transcriptional Co-activators Mediates Binding to Nuclear Receptors,” Nature, vol. 387, pp. 733-736, 1997.
Henttu et al., “AF-2 Activity and Recruitment of Steroid Receptor Coactivator 1 to the Estrogen Receptor Depend on a Lysine Residue Conserved in Nuclear Receptors,” Molecular and Cellular Biology, vol. 17, No. 4, pp. 1832-1839, 1997.
Hong et al., “GRIP1, a Novel Mouse Protein That Serves as a Transcriptional Coactivator in Yeast for the Hormone Binding Domains of Steroid Receptors,” Proc. Natl. Acad. Sci. USA, vol. 93, pp. 4948-4952, 1996.
Hong et al., “GRIP1, a Transcriptional Coactivator for the AF-2 Transactivation Domain of Steroid, Thyroid, Retinoid, and Vitamin D Receptors,” Molecular and Cell Biology, vol. 17, No. 5, pp. 2735-2744, 1997.
Horwitz et al., “Nuclear Receptor Coactivators and Corepressors,” Molecular Endocrinology, vol. 10, pp. 1167-1177, 1996.
Janknetcht et al., “Rapid and Efficient Purification of Native Histidine-tagged Protein Expressed by Recombinant Vaccinia Virus,” Proc. Natl. Acad. Sci. USA, vol. 88, pp. 8972-8976, 1991.
Jurutka et al., “Mutations in the 1,25-Dihydroxyvitamin D3Receptor Identifying C-Terminal Amino Acids Required for Transcriptional Activation That are Functionally Dissociated from Hormone Binding, Heterodimeric DNA Binding, and Interaction with Basal Transcription Factor IIB, in Vitro,” J. Biol. Chem., vol. 272, No. 23, pp. 14592-14599, 1997.
Kakizawa et al., “Ligand-dependent Heterodimerization of Thyroid Hormone Receptor and Retinoid X Receptor,” J. of Biol. Chem., vol. 272, No. 38, pp. 23799-23804, 1997.
Kamei et al., “A CBP Integrator Complex Mediates Transcriptional Activation and AP-1 Inhibition by Nuclear Receptors,” Cell, vol. 85, pp. 403-414, 1996.
Kuiper et al., “Comparison of the Ligand Binding Specificity and Transcript Tissue Distribution of Estrogen Receptors α and β,” Endocrinology, vol. 138, No. 3, pp. 863-870, 1997.
Kuntz, “Structure-Based Strategies for Drug Design and Discovery ,” Science, vol. 257, pp. 1078-1082, 1992.
Kussie et al., “Structure of the MDM2 Oncoprotein Bound to the p53 Tumor Suppressor Transactivation Domain,” Science, vol. 274, pp. 948-953, 1996.
Landel et al., “Estrogen Receptor Accessory Proteins Augment Receptor-DNA Interaction and DNA Bending,” J. Steroid Biochem. Molec. Bio., vol. 63, pp. 59-73, 1997.
Landel et al., “The Interaction of Human Estrogen Receptor with DNA Is Modulated by Receptor-Associated Proteins,” Molecular Endorinology, vol. 8, pp. 1407-1419, 1994.
Lanzennec et al., “Mechanistic Aspects of Estrogen Receptor Activation Probed with Constitutively Active Estrogen Receptors: Correlations with DNA and Coregulator Interactions and Receptor Conformational Changes,” Molecular Endocrinology, vol. 11, pp. 1375-1386, 1997.
Le Douarin et al., “A Possible Involvement TIF1α and TIF1β in the Epigenetic Control of Transcription by Nuclear Receptors,” EMBO J., vol. 15, No. 23, pp. 6701-6715, 1996.
Lee et al., “Thyroid Hormone Receptor Dimerizati
Baxter John D.
Darimont Beatrice
Feng Weijun
Fletterick Robert J.
Kushner Peter J.
Moran Marjorie
Morgan & Lewis & Bockius, LLP
The Regents of the University of California
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