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AssigneeNational University of Singapore
InventorsPonnampalam Gopalakrishnakone, Maung-Maung Thwin, Kandiah Jeyaseelan, Arunmozhiarasi Armugam
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A phospholipase A2 inhibitor protein designated “Phospholipase Inhibitor from Python” (PIP)—formerly designated “Python Antitoxic Factor” (PAF)—is given by SEQ ID NO:2. The partial amino acid sequence for PIP was initially determined from the native protein purified from the blood serum of a non-venomous snake, Python reticulatus. The complete PIP polynucleotide sequence was obtained from a cDNA clone encoding PIP, given by SEQ ID NO:1, along with the full amino acid sequence deduced from it. Also disclosed is a recombinant protein PIP, which shows strong lethal toxin neutralizing activity similar to the native PIP, and has potent anti-inflammatory activity. Both the native and the functionally equivalent recombinant PIP are useful for the prevention or treatment of conditions such as snakebites, insect stings, and inflammatory diseases. Also, phospholipase A2 (PLA2) inhibitory polypeptides designated P-0029, P-0009, and P-0006, the sequences of which are given as SEQ ID NO:10, SEQ ID NO:11, and SEQ ID NO:12, respectively, are disclosed. Those polypeptides, and their synthetic chemical analogues and polypeptide variants that inhibit PLA2 activity and alleviate inflammation, may also be used in the diagnosis, study, prevention, and treatment of PLA2-related human inflammatory diseases.
An isolated polypeptide comprising the sequence set forth in SEQ ID NO:6, or a fragment thereof having at least 10 contiguous amino acids including the tetrapeptide proline-glycine-leucine-proline and having activity as a phospholipase A2 inhibitor, or a variant thereof having one or more conservative amino acid substitutions while retaining the tetrapeptide proline-glycine-leucine-proline, said variant having activity as a phospholipase A2 inhibitor, wherein said polypeptide is at least 85% homologous to the polypeptide of SEQ ID NO:6.
A polypeptide consisting essentially of the amino acid sequence set forth in SEQ ID NO:10.
A polypeptide consisting essentially of the amino acid sequence set forth in SEQ ID NO:11.
A method of producing a polypeptide variant of a parent polypeptide comprising the sequence set forth in SEQ ID NO:2 or SEQ ID NO:6, comprising the steps of:
Dependencies are inferred from the claim text.