Study of gamma interferon agonists/mimetics

University Of Florida, Gainesville FL

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Abstract

Gamma interferon (IFN_() is an essential cytokine for mediation of functions that are obligatory for good health, particularly that mediated through or maintained through CD4 T- helper 1 (Thl) cells. Further, IFN_, possesses direct antiviral and anticellular (antitumor) activity. Thus, the development of IFN1, mimetics has important implications for immune- therapy in infectious diseases and cancer. The Specific Aims listed below directly test both the rational development of such mimetics as well as their use in the mediation of IFN_, activity. 1. Synthesis of IFN1, peptide mimetics based on sequence and structural similarity to biologically active IFNI, C-terminal peptides. 2. Compare several methods for delivery of IFN_, peptides intracellularly, including chemical modification and use of molecular expression systems. 3. Determine signaling function of IFN_, peptide mimetics in terms of JAK/STAT activation, upregulation of tumor suppressor gene p21 wAF/cIP, and down regulation of neu/HER-2 protooncogene in cancer cells. 4. Determine cellular function of IFN_, peptide mimetics in terms of antiviral activity, anticellular (antitumor) activity, and upregulation of MHC class II molecules. 5. Determine biological activity of IFN_, mimetic peptides in mouse models of virus infection and cancer.