Novel purified polypeptides from Streptococcus pneumoniae
AssigneeAffinium Pharmaceuticals, Inc.
InventorsAled Edwards, Akil Dharamsi, Masoud Vedadi, Teresa Clarke, Matthew Kimber, Vivek Sharma, Simon Houston, Kamran Mansoury
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Abstract
The present invention relates to novel drug targets for pathogenic bacteria. Accordingly, the invention provides purified protein comprising the amino acid sequence set forth in SEQ ID NO: 4. The invention also provides biochemical and biophysical characteristics of the polypeptides of the invention.
Claims20
A composition comprising an isolated, recombinant polypeptide, wherein the polypeptide comprises:
- (a) an amino acid sequence set forth in SEQ ID NO:
- 2 or SEQ ID NO:
- 4;
- (b) an amino acid sequence having at least about 95% identity with the amino acid sequence set forth in SEQ ID NO:
- 2 or SEQ ID NO:
- 4;
- or (c) an amino acid sequence encoded by a polynucleotide that hybridizes under stringent conditions to the complementary strand of a polynucleotide having SEQ ID NO:
- 1 or SEQ ID NO:
- 3 and has at least one biological activity of guanylate kinase from S. pizeumoniae;
- and wherein the polypeptide of (a), (b) or (c) is at least about 90% pure in a sample of the composition.
A method for identifying a modulator of a polypeptide, the method comprising:
- (a) providing the three-dimensional coordinates for a plurality of the amino acids of a polypeptide comprising (1) an amino acid sequence set forth in SEQ ID NO:
- 2 or SEQ ID NO:
- 4;
- (2) an amino acid sequence having at least about 95% identity with the amino acid sequence set forth in SEQ ID NO:
- 2 or SEQ ID NO:
- 4;
- or (3) an amino acid sequence encoded by a polynucleotide that hybridizes under stringent conditions to the complementary strand of a polynucleotide having SEQ ID NO:
- 1 or SEQ ID NO:
- 3 and has at least one biological activity of guanylate kinase from S. pneumoniae;
- (b) identifying a druggable region of the polypeptide;
- and
- (c) selecting at least one potential modulator by using the three dimensional coordinates to determine if a chemical entity may bind to or interfere with the druggable region.
A method for designing a modulator for the prevention or treatment of a S. pneumoniae related disease or disorder, comprising:
- (a) providing the three-dimensional coordinates for a plurality of the amino acids of a polypeptide comprising (1) an amino acid sequence set forth in SEQ ID NO:
- 2 or SEQ ID NO:
- 4;
- (2) an amino acid sequence having at least about 95% identity with the amino acid sequence set forth in SEQ ID NO:
- 2 or SEQ ID NO:
- 4;
- or (3) an amino acid sequence encoded by a polynucleotide that hybridizes under stringent conditions to the complementary strand of a polynucleotide having SEQ ID NO:
- 1 or SEQ ID NO:
- 3 and has at least one biological activity of guanylate kinase from S. pneumoniae;
- and
- (b) designing a potential modulator for the prevention or treatment of a S. pneumoniae related disease or disorder by employing the three-dimensional structure in a rational drug design method.
Dependencies are inferred from the claim text.