NOVEL THERAPEUTIC AND PROPHYLACTIC AGENTS AND METHODS OF USING SAME

摘要

A phospholipase A2 inhibitor protein designated "Phospholipase inhibitor from Python" (PIP), formerly designated "Python Antitoxic Factor" (PAF), the partial amino acid sequence for which was initially determined from the native protein purified from the blood serum of a nonvenomous snake, Python reticulatus, and given by SEQ ID NO:1. The complete PAF polynucleotide sequence was obtained from a cDNA clone encoding PIP (or PAF), and given by SEQ ID NO:2 along with the full amino acid sequence deduced from it. Also a recombinant protein PIP (or PAF) which shows strong lethal toxin neutralizing activity similar to the native PIP (or PAF), and has potent anti-inflammatory activity. Both the native and the functionally equivalent recombinant PIP (or PAF) are useful for the prevention or treatment of conditions such as snakebites, insect stings, and inflammatory diseases. Also, a potent phospholipase A2 (PLA2) inhibitory polypeptide designated P-0029 (SEQ ID NO:10), and moderately active PLA2-inhibitory polypeptides, P-0009 and P-0006, the sequences of which are given as SEQ ID NO:11 and SEQ ID NO:12, respectively. Those polypeptides, and their synthetic chemical analogues, or 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.