PURIFICATION AND CHARACTERIZATION OF A TNF INHIBITOR

THE OVERALL OBJECTIVE IS TO PURIFY A NOVEL TUMOR NECROSIS FACTOR (TNF)-INHIBITING PEPTIDE (TNFI) AND ANALYZE ITS POTENTIAL THERAPEUTIC VALUE. THE PHASE I OBJECTIVE IS TO PURIFY AND DETERMINE THE AMINO ACID SEQUENCE OF TNFI. CULTURE SUPERNATANTS HARVESTED FROM A TRANSFORMED CELL LINE WILL BE SUBJECTED TO STANDARD PROTEIN PURIFICATION PROCEDURES TO ACCOMPLISH THIS GOAL. THIS WILL PROVIDE THE BASIS FOR FUTURE WORK IN CLONING THE TNFI GENE AND/OR SYNTHESIZING THE PEPTIDE IN ORDER TO PERFORM IN VITRO AND IN VIVO FUNCTIONAL STUDIES. ULTIMATELY, RECOMBINANT OR SYNTHETIC TNFI WILL BE TESTED IN VARIOUS ANIMAL MODELS TO ANALYZE ITS THERAPEUTIC VALUE IN CERTAIN DISEASES. EVIDENCE IS RAPIDLY ACCUMULATING IMPLICATING TNF AS A MEDIATOR OF THE PATHOLOGY SEEN IN CONDITIONS SUCH AS SEPTIC SHOCK, CACHEXIA, AIDS, MALARIA, ADULT RESPIRATORY DISTRESS SYNDROME, RHEUMATOID ARTHRITIS, MYOCARDIAL INFARCTION, ALLOGRAFT REJECTION, GRAFT VERSUS HOST DISEASE, AND SUPPRESSION OF HEMATOPOIESIS.