Title:
METHODS AND KITS FOR DISCOVERY OF RNA-BINDING COMPOUNDS
Document Type and Number:
WIPO Patent Application WO1999064625
Kind Code:
A3
Abstract:
The invention relates to a solution-based assay for identifying RNA binding compounds, based on competition. The assay comprises a reporter molecule carrying a fluorescent or chromogenic group that can form a one-to-one complex with an RNA target molecule carrying a second fluorescent or chromogenic group in such a way that the two groups are in sufficient proximity for fluorescence resonance energy transfer and/or quenching to take place. Addition of a compound-to-be-tested prevents formation of the complex and thereby increases the fluorescence of the RNA target and/or reporter molecules relative to the signal obtained in the absence of the test compound. The invention also provides for quantitative screening methods and kits are also included.
Inventors:
KARN JONATHAN (GB)
PRESCOTT CATHERINE DENISE (GB)
PRESCOTT CATHERINE DENISE (GB)
Application Number:
PCT/GB1999/001761
Publication Date:
August 23, 2001
Filing Date:
June 04, 1999
Export Citation:
Assignee:
RIBOTARGETS LTD (GB)
International Classes:
G01N33/53; C12N15/09; C12Q1/68; C12Q1/70; G01N21/78; G01N33/542; G01N33/566; G01N37/00
Domestic Patent References:
| WO1997009342A1 | 1997-03-13 | |||
| WO1997043444A1 | 1997-11-20 | |||
| WO1994029487A1 | 1994-12-22 | |||
| WO1992002228A1 | 1992-02-20 | |||
| WO1998039484A1 | 1998-09-11 | |||
| WO1999009056A1 | 1999-02-25 |
Foreign References:
| US5593835A | 1997-01-14 |
Other References:
WANG Y ET AL.: "Specificity of aminoglycoside binding to RNA constructs derived from the 16S rRNA decoding region and the HIV-RRE activator region", BIOCHEMISTRY, vol. 36, 1997, pages 768 - 779, XP002120808
CARDULLO R A ET AL: "DETECTION OF NUCLEIC ACID HYBRIDIZATION BY NONRADIATIVE FLUORESCENCE RESONANCE ENERGY TRANSFER", PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF USA, vol. 85, no. 23, 1 December 1988 (1988-12-01), pages 8790 - 8794, XP000453537, ISSN: 0027-8424
CHURCHER M J ET AL.: "High affinity binding of TAR RNA by the human immunodeficiency virus type-1 tat protein requires base-pairs in the RNA stem and amino acid residues flanking the basic region", JOURNAL OF MOLECULAR BIOLOGY, vol. 230, 1993, pages 90 - 110, XP002120809
METZGER A U ET AL.: "The interaction of HIV-1 Tat(32-72) with its target RNA: A fluorescence and nuclear magnetic resonance study", BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, vol. 241, 1997, pages 31 - 36, XP002120810
H -Y- MEI ET AL: "Discovery of Selective, Small-Molecule Inhibitors of RNA Complexes - I. The Tat Protein/TAR RNA Complexes Required for HIV-1 Transcription", BIOORGANIC & MEDICINAL CHEMISTRY, vol. 5, no. 6, 1 January 1997 (1997-01-01), pages 1173 - 1184, XP002096444, ISSN: 0968-0896
CALNAN B J ET AL.: "Analysis of arginine-rich peptides from the HIV Tat protein reveals unusual features of RNA-protein recognition", GENES & DEVELOPMENT, vol. 5, 1991, pages 201 - 210, XP002120811
CARDULLO R A ET AL: "DETECTION OF NUCLEIC ACID HYBRIDIZATION BY NONRADIATIVE FLUORESCENCE RESONANCE ENERGY TRANSFER", PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF USA, vol. 85, no. 23, 1 December 1988 (1988-12-01), pages 8790 - 8794, XP000453537, ISSN: 0027-8424
CHURCHER M J ET AL.: "High affinity binding of TAR RNA by the human immunodeficiency virus type-1 tat protein requires base-pairs in the RNA stem and amino acid residues flanking the basic region", JOURNAL OF MOLECULAR BIOLOGY, vol. 230, 1993, pages 90 - 110, XP002120809
METZGER A U ET AL.: "The interaction of HIV-1 Tat(32-72) with its target RNA: A fluorescence and nuclear magnetic resonance study", BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, vol. 241, 1997, pages 31 - 36, XP002120810
H -Y- MEI ET AL: "Discovery of Selective, Small-Molecule Inhibitors of RNA Complexes - I. The Tat Protein/TAR RNA Complexes Required for HIV-1 Transcription", BIOORGANIC & MEDICINAL CHEMISTRY, vol. 5, no. 6, 1 January 1997 (1997-01-01), pages 1173 - 1184, XP002096444, ISSN: 0968-0896
CALNAN B J ET AL.: "Analysis of arginine-rich peptides from the HIV Tat protein reveals unusual features of RNA-protein recognition", GENES & DEVELOPMENT, vol. 5, 1991, pages 201 - 210, XP002120811
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