Prokineticin polypeptides, related compositions and methods
AssigneeThe Regents of the University of California
InventorsQun-Yong Zhou, Frederick J. Ehlert
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Abstract
The invention provides isolated polypeptides that stimulate gastrointestinal smooth muscle contraction, including human prokineticin 1 and human prokineticin 2 polypeptides, and functional fragments and modifications thereof. Also provided are methods of stimulating gastrointestinal smooth muscle contraction in a mammal, by administering to the mammal an effective amount of a prokineticin polypeptide. The invention also provides nucleic acid molecules encoding a prokineticin polypeptide, and antibodies that selectively bind a prokineticin polypeptide. Further provided are methods of identifying a prokineticin receptor ligand, agonist or antagonist.
Claims52
An isolated polypeptide that stimulates gastrointestinal smooth muscle contraction, comprising an amino acid sequence at least 80% identical to the sequence of human prokineticin 1 (SEQ ID NO:3), said sequence comprising the N-terminal 6 amino acids of SEQ ID NO:3, the 10 conserved cysteine residues of SEQ ID NO:3, and from 0 to 9 of the 9 C-terminal amino acids of SEQ ID NO:3.
An isolated peptide comprising at least 10 contiguous amino acids of SEQ ID NO:3, wherein said peptide is immunogenic.
An isolated polypeptide that stimulates gastrointestinal smooth muscle contraction, comprising an amino acid sequence at least 80% identical to the sequence of human prokineticin 2 (SEQ ID NO:6), said sequence comprising the N-terminal 6 amino acids of SEQ ID NO:6, the 10 conserved cysteine residues of SEQ ID NO:6, and from 0 to 4 of the 4 C-terminal amino acids of SEQ ID NO:6.
An isolated peptide comprising at least 10 contiguous amino acids of SEQ ID NO:6, wherein said peptide is immunogenic.
A method of identifying a prokineticin receptor ligand, comprising contacting a preparation comprising prokineticin receptor with one or more candidate compounds, and identifying a compound that specifically binds to said receptor, said compound being characterized as a prokineticin receptor ligand.
A method of identifying a prokineticin receptor agonist, comprising contacting a preparation comprising a prokineticin receptor with one or more candidate compounds, and identifying a compound that selectively promotes production of a prokineticin receptor signal, said compound being characterized as a prokineticin receptor agonist.
A method of identifying a prokineticin receptor antagonist, comprising contacting a preparation comprising a prokineticin receptor with one or more candidate compounds in the presence of a prokineticin, and identifying a compound that selectively inhibits production of a prokineticin receptor signal, said compound being characterized as a prokineticin receptor antagonist.
Dependencies are inferred from the claim text.