Study of gamma interferon agonists/mimetics

γ干扰素激动剂/模拟物的研究

• 批准号: 6798822
• 负责人: HOWARD M JOHNSON
• 金额: $ 32.7万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-15 至 2007-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6798822
• 关键词: MHC class II antigen; athymic mouse; biomimetics; enzyme activity; interferon gamma; neoplastic growth; oncoprotein p21; peptide structure; protein sequence; protein tyrosine kinase; protooncogene; stimulant /agonist; synthetic peptide; tumor suppressor genes

DESCRIPTION (provided by applicant): Gamma interferon (IFNgamma) is an essential cytokine for mediation of functions that are obligatory for good health, particularly that mediated through or maintained through CD4 T helper1 (Th1) cells. Further, IFNgamma possesses direct antiviral and anticellular (antitumor) activity. Thus, the development of IFNgamma 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 IFNgamma activity. 1. Synthesis of IFNgamma peptide mimetics based on sequence and structural similarity to biologically active IFNgamma C-terminal peptides. 2. Compare several methods for delivery of IFNgamma peptides intracellularly, including chemical modification and use of molecular expression systems. 3. Determine signaling function of IFNgamma peptide mimetics in terms of JAK/STAT activation, upregulation of tumor suppressor gene p21WAF/CIP, and down regulation of neu/HER-2protooncogene 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 IFNgamma mimetic peptides in mouse models of virus infection and cancer.

说明（由申请人提供）： γ 干扰素 (IFNgamma) 是调节健康所必需的功能的重要细胞因子，特别是通过 CD4 T 辅助 1 (Th1) 细胞介导或维持的功能。此外，IFNγ具有直接的抗病毒和抗细胞（抗肿瘤）活性。因此，IFNγ模拟物的开发对于传染病和癌症的免疫治疗具有重要意义。下面列出的具体目标直接测试此类模拟物的合理开发及其在 IFNγ 活性介导中的用途。 1.基于与生物活性IFNγC端肽的序列和结构相似性合成IFNγ肽模拟物。 2. 比较几种细胞内递送 IFNγ 肽的方法，包括化学修饰和分子表达系统的使用。 3.确定IFNγ肽模拟物在癌细胞中JAK/STAT激活、抑癌基因p21WAF/CIP上调和neu/HER-2原癌基因下调方面的信号传导功能。 4. 确定IFN的细胞功能？肽模拟物的抗病毒活性、抗细胞（抗肿瘤）活性和 MHC II 类分子的上调。 5. 确定 IFNgamma 模拟肽在病毒感染和癌症小鼠模型中的生物活性。