Sequence-directed DNA-binding molecules compositions and methods
The present invention defines a DNA: protein-binding assay useful for screening libraries of synthetic or biological compounds for their ability to bind DNA test sequences. The assay is versatile in that any number of test sequences can be tested by placing the test sequence adjacent to a defined pr...
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Format | Patent |
Language | English |
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22.03.2005
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Abstract | The present invention defines a DNA: protein-binding assay useful for screening libraries of synthetic or biological compounds for their ability to bind DNA test sequences. The assay is versatile in that any number of test sequences can be tested by placing the test sequence adjacent to a defined protein binding screening sequence. Binding of molecules to these test sequence changes the binding characteristics of the protein molecule to its cognate binding sequence. When such a molecule binds the test sequence the equilibrium of the DNA:protein complexes is disturbed, generating changes in the concentration of free DNA probe. Numerous exemplary target test sequences (SEQ ID NO:1 to SEQ ID NO:600) are set forth. The assay of the present invention is also useful to characterize the preferred binding sequences of any selected DNA-binding molecule. |
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AbstractList | The present invention defines a DNA: protein-binding assay useful for screening libraries of synthetic or biological compounds for their ability to bind DNA test sequences. The assay is versatile in that any number of test sequences can be tested by placing the test sequence adjacent to a defined protein binding screening sequence. Binding of molecules to these test sequence changes the binding characteristics of the protein molecule to its cognate binding sequence. When such a molecule binds the test sequence the equilibrium of the DNA:protein complexes is disturbed, generating changes in the concentration of free DNA probe. Numerous exemplary target test sequences (SEQ ID NO:1 to SEQ ID NO:600) are set forth. The assay of the present invention is also useful to characterize the preferred binding sequences of any selected DNA-binding molecule. |
Author | Turin, Lisa M Fry, Kirk E Edwards, Cynthia A Andrews, Beth M Cantor, Charles R |
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References | Richardson et al. (4257774) 19810300 Edwards et al. (5726014) 19980300 Crooke et al. (4270924) 19810600 (WO 8806601) 19880900 (WO 9220698) 19921100 Edwards et al. (5744131) 19980400 (WO 9300446) 19930100 Hobson, K., Use of DNA-Protein Interaction to Isolate Specific Genomic DNA Sequences, Analytical Biochemistry, 193:220-224 (1991). Edwards et al. (6010849) 20000100 Ray, R., et al., "Mithramycin Blocks Protein Binding and Function of the SV40 Early Promoter," J. Clin. Invest. 83:2003-2007 (1989). Evans et al. (5071773) 19911200 Van Dyke, M.W., et al., Chromomycin, Mithramycin, and Olivomycin Binding Sites on Heterogeneous Deoxyribonucleic Acid-Footprinting with (Methidiumpropyl-EDTA) ironiii), Biochemistry 22:2273-2377 (1983). Edwards et al. (6384208) 20020500 Ladner et al. (5096815) 19920300 Snyder, R.C., et al., "Mithramycin Blocks Transcriptional Initiation of the c-myc P1 and P2 Promoters," Biochemistry 30:4290-4297 (1991). Huang, C.-C., Triple-Helix Formation Is Compatible with an Adjacent DNA-Protein Complex, Biochemistry, 31:993-998 (1992). Edwards et al. (5693463) 19971200 Hanvey, J.C., et al., "Site-Specific Inhibition of EcoRi Restriction/Modification Enzymes by a DNA Triple Helix," Nuc. Acids Res. 18(1):157-161 (1990). Debart, F., et al., "Synthesis, DNA Binding, and Biological Evaluation of Synthetic Precursors and Novel Analogues of Netropsin," J. Med. Chem. 32: 1074-1083 (1989). (WO 8704170) 19870700 McGeoch, D.J., et al., "The Complete DNA Sequence of the Long Unique Region in the Genome of the Herpes Simplex Virus Type 1," J. Gen. Virol. 69:1531-1574 (1988). Edwards et al. (5738990) 19980400 Davison, A.J., et al., "The Complete DNA Sequence of Varicella-Zoster Virus," J. Gen. Virol. 67:1759-1816 (1986). Edwards et al. (5306619) 19940400 Miller et al. J. Clin. Invest. 83:2003-2007 (1989). Edwards et al. (5578444) 19961100 Zein, N., et al., "Calicheamicin γ11: An Antitumor Antibiotic That Cleaves Double-Stranded DNA Site Specifically," Science 240:1198-1201 (1988). |
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