Therapeutic and prophylactic agents and methods of using the same

摘要

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.