Polypeptide Fragments Comprising Endonuclease Activity and Their Use
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United States of America Patent
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app pub date -
Dec 18, 2009
filing date -
Dec 19, 2008
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Abstract
The present invention relates to polypeptide fragments comprising an amino-terminal fragment of the PA subunit of a viral RNA-dependent RNA polymerase or variants thereof possessing endonuclease activity, wherein said PA subunit is from a virus belonging to the Orthomyxoviridae family. This invention also relates to (i) crystals of the polypeptide fragments which are suitable for structure determination of said polypeptide fragments using X-ray crystallography and (ii) computational methods using the structural coordinates of said polypeptide to screen for and design compounds that modulate, preferably inhibit the endonucleolytically active site within the polypeptide fragment. In addition, this invention relates to methods identifying compounds that bind to the PA polypeptide fragments possessing endonuclease activity and preferably inhibit said endonucleolytic activity, preferably in a high throughput setting. This invention also relates to compounds and pharmaceutical compositions comprising the identified compounds for the treatment of disease conditions due to viral infections caused by viruses of the Orthomyxoviridae family.
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- A61K:PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOS....
- C12Q:MEASURING OR TESTING PROCESSES INVOLVING ENZYMES O....
- C12N:MICRO-ORGANISMS OR ENZYMES; COMPOSITIONS THEREOF
- C07C:ACYCLIC OR CARBOCYCLIC COMPOUNDS
- A61P:THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDI....
- G06G:ANALOGUE COMPUTERS
- C40B:COMBINATORIAL CHEMISTRY; LIBRARIES, e.g. CHEMICAL ....
- C07K:PEPTIDES
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