Chemistry: molecular biology and microbiology – Measuring or testing process involving enzymes or...
Reexamination Certificate
2003-11-10
2008-09-02
Robinson, Hope A (Department: 1652)
Chemistry: molecular biology and microbiology
Measuring or testing process involving enzymes or...
C435S006120, C435S007100
Reexamination Certificate
active
07419780
ABSTRACT:
A method for identifying a protein as being able to bind a ligand comprising, providing a molecule composed of a methotrexate moiety that is covalently bonded to the ligand; introducing the molecule into a cell which a) expresses a first fusion protein comprising a dihydrofolate reductase capable of binding methotrexate, expresses b) a second fusion protein comprising the protein, wherein one of the first and second fusion proteins also comprises a transcription activator domain and the other comprises a DNA-binding domain, and c) has a reporter gene wherein expression of the reporter gene is conditioned on the proximity of the first fusion protein to the second fusion protein; permitting the molecule to bind to the first fusion protein and to the second fusion protein so as to activate the expression of the reporter gene; and selecting the cell if it expresses the reporter gene.
REFERENCES:
patent: 5194594 (1993-03-01), Kwawli et al.
patent: 5314817 (1994-05-01), Schultz
patent: 5468614 (1995-11-01), Fields et al.
patent: 5736343 (1998-04-01), Landry
patent: 5925523 (1999-07-01), Dove et al.
patent: 5928868 (1999-07-01), Liu et al.
patent: 6030785 (2000-02-01), Katze et al.
patent: 6200759 (2001-03-01), Dove et al.
patent: 7083918 (2006-08-01), Althoff et al.
patent: 2002/0168685 (2002-11-01), Cornish
patent: 2003/0138785 (2003-07-01), Kopytek et al.
patent: 2003/0203471 (2003-10-01), Althoff et al.
patent: 0742015 (1996-11-01), None
patent: 9731113 (1997-08-01), None
patent: 9813353 (1998-04-01), None
patent: 9910508 (1999-03-01), None
patent: 9910510 (1999-03-01), None
patent: 9630540 (1999-10-01), None
patent: WO02059272 (2002-08-01), None
patent: WO03060073 (2003-11-01), None
patent: WO2004042345 (2004-05-01), None
Abida et al. (ChemBioChem, 2002, vol. 3, pp. 887-895).
Austin DJ, et al. Proximity versus allostery: the role of regulated protein dimerization in biology. 1994. Chem Biol. 1(3): 131-6.
Belshaw PJ, et al. Controlling protein association and subcellular localization with a synthetic ligand that induces heterodimerization of proteins. 1996. Proc. Natl Acad Sci USA 93(10):4604-7.
Belshaw PJ, et al. Controlling programmed cell death with a cyclophilin-cyclosporin-based chemical inducer of dimerization. 1996. Chem. Biol. 3:731-738.
Choi J, et al. Structure of the FKBP-12-Rapamycin complex interacting with the binding domain of human FRAP. 1996. Science 273(5272):239-42.
DeGrado WF, et al. Screening, selection and design: standing at the crossroads in three dimensions. 1997. Current Opinion in Structural Biology 7:455-456.
Diver SR, et al. Single-step synthesis of cell-permeable protein dimerizers that activate signal transduction and gene expression. 1997. J. Am. Chem. Soc. 119: 5106-5109.
Ho SN, et al. Dimeric ligands define a role for transcriptional activation domains in reinitiation. 1996. Nature. 382(6594):822-6.
Holsinger LJ, et al. Signal transduction in T lymphocytes using a conditional allele of Sos. 1995. Proc. Natl. Acad. Sci. USA 92:9810-9814.
Hung DT, et al. Understanding and controlling the cell cycle with natural products. 1996. Chem. Biol. 3:623-639.
Klemm JD, et al. Dimerization as a regulatory mechanism in signal transduction. 1998. Annu. Rev. Immunol. 16:569-92.
Liberles SD, et al. Inducilble gene expression and protein translocation using nontoxic ligands identified by a mammalian three-hybrid screen. 1997. Proc. Natl. Acad. Sci. USA 94(15):7825-7830.
Licitra EJ, et al. A three-hybrid system for detecting small ligand-protein receptor interactions. 1996. Proc. Natl. Acad. Sci. USA 98:12817-12821.
Pedersen H, et al. A method for directed evolution and functional cloning of enzymes. 1998. Proc. Natl. Acad. Sci. USA 95:10523-10528.
Pruschy MN, et al. Mechanistic studies of a signaling pathway activated by the organic dimerizer FK1012. 1994. Cbem. Biol. 1:163-172.
Schreiber SL. Chemical genetics resulting from a passion for synthetic organic chemistry. 1998. Bioorganic & Medicinal Chemistry 6:1127-1152.
Spencer DM , et al. Controlling signal transduction with synthetic ligands. 1993. Science 262(5136):1019-1024.
Spencer DM, et al. Functional analysis of Fas signaling in vivo using synthetic inducers of dimerization. 1996. Curr Biol. 6(7):839-47.
Spencer DM, et al. A general strategy for producing conditional alleles of Src-like tyrosine kinases. 1995. Proc. Natl. Acad. Sci. 92:9805-9809.
Stockwell BR, et al. TGF-beta-signaliung with small molecule FKBP12 antagonists that bind myristoylated FKBP12- TGF-beta type 1 receptor fusion proteins. 1998. Chem Biol. 5(7):385-95.
Stockwell BR, et al. Probing the role of homomeric and heteromeric receptor interactions in TGF-beta signaling using small molecule dimerizers.1998. Curr Biol 8(13):761- 70.
Winkler T., et al. Confocal fluorescence coincidence analysis: An approach to ultra high-throughput screening. 1998 Proc. Natl. Acad. Sci. USA 96:1375-1378.
Yang, J., et al. Small-molecule control of insulin and PDGF receptor signaling and the role of membrane attachment. 1997 Curr. Biol. 8:11-18.
Zlokarnik G, et al. Quatitation of tranmscription and clonal selection of single living cells with beta-lactamase as reporter. 1998, Science 279(5347):84-8.
Search Report dated May 14, 2001 corresponding PCT International Application No. PCT/US01/02285.
Amara, J. F. et al. : A versatile synthetic dimerizer for the regulation of protein-protein interactions, Proc. Natl. Acad. Sci. USA, vol. 94, 1997, pp. 10618-10623.
PCT International Search Report dated Jul. 17, 2003 corresponding to PCT International Application No. PCT/US02/40943.
Pollock et al. Demerizer-regulated gene expression. Current Opinion in Biotechnology (2002) 13:459-467.
Lin, H., et al. Dexamethasone-Methotrexate: An Efficient Chemical Inducer of Protein Dimerization In Vivo. 2000. J.Am.Chem.Soc. 122:4247-4248.
Kopytek, S.J., et al. Chemically Induced Dimerization of Dihydrofolate Reductase by a Homobifunctional Dimer of Methotrexate. 2000. Chem Biol. 7:313-321.
Firestine, S.M., et al. Using an AraC-Based three-hybrid system to detect biocatalysts in vivo. 2000. Nature Biotechnology. 18, 544-547.
Pelletier, J.N., et al. Oligomerization domain-directed reassembly of active dihydrofolate reductase from rationally designed fragments. 1998. Proc.Natl.Acad.Sci.USA. 95, 12141-12146.
Ladant, D., Karimova, G. Genetic systems for analyzing protein-protein interactions in bacteria. 2000. Res. Microbiol. 151, 711-720.
Dove et al., (1997) “Activation of Prokaryotic Transcription Through Arbitrary Protein-Protein Contacts”Nature386:627-630 ; and.
Filman et al., (1982) “Crystal Structures ofEscherichia coliandLactobacillus caseiDihydrofolate Reductase Refined at 1.7 A Resolution”,The Journal of biological Chemistry257(22): 13663-13672.
Written Opinion, published Mar. 20, 2003, corresponding to PCT International Application Publication No. WO 02/059272 A3.
Supplementary Partial European Search Report issued Apr. 19, 2005 in connection with the counterpart European Application No. 01942644.4.
Cornish, Virginia W. et al., “Dexamethasone-Methotrexate: An Efficient Chemical Inducer Of Protein Dimerization In Vivo,”Abstracts of Papers American Chemical Society, vol. 219, No. 1-2, p. BIOL 124 (2000).
Cornish, Virginia W. et al., “Synthesis of Dexamethasone-Methotrexate CIDS With Variable Linkers,”Book of Abstracts, American Chemical Society, 219thACS National Meeting, San Francisco, CA, p. CHED 401 (Mar. 26-30, 2000).
Griffith, E.C. et al. “Yeast Three-Hybrid System for Detecting Ligand-Receptor Interactions,”Methods in Enzymology, vol. 328, pp. 89-103 (2000).
Simons, S. et al., (1981) Dexamethasone 21-mesylate: an affinity label of glucocorticoid receptors from rat hepatoma tissue culture cells,Biochemistry78 (6) : 3541-3545.
Fan, J. et al. (1989) Covalent labeling of dihydrofolate reductase and folate transport proteins by fluorescein methotrexate, chemistry and biology of pteridines,1990 Walter de Gruyter & Co., pp. 1162-1165.
Lin et al. (2000) “Dexamethasone 21-mesylate: an efficient chemi
Cooper & Dunham LLP
Robinson Hope A
The Trustees of Columbia University in the City of New York
White John P.
LandOfFree
Methods and assays for screening protein targets does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Methods and assays for screening protein targets, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Methods and assays for screening protein targets will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-3979183