OXIDANT EFFECTS IN MALARIA INFECTED ERYTHROCYTES

疟疾感染红细胞的氧化作用

• 批准号: 2848267
• 负责人: Steven Richard Meshnick
• 金额: $ 23.95万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-01-01 至 2001-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2848267
• 关键词: Plasmodium falciparum; alkylation; antimalarial agents; binding proteins; chemical structure function; drug interactions; drug metabolism; electrospray ionization mass spectrometry; erythrocytes; free radicals; gas chromatography mass spectrometry; human tissue; immunoelectron microscopy; immunofluorescence technique; immunoprecipitation; intracellular parasitism; malaria; parasitic disease chemotherapy; polymerase chain reaction; protein binding; protein engineering; site directed mutagenesis

DESCRIPTION (Adapted from the Applicant's Abstract): Dr. Meshnick and co-workers have identified one of the artemisinin target proteins as a Translationally Controlled Tumor Protein (TCTP) homolog. This Plasmodium falciparum TCTP has been cloned and sequenced, and purified recombinant TCTP has been obtained. Antibody to recombinant TCTP immunoprecipitates (3H) dihydroartemisinin-TCTP complex from drug-treated parasites. Aim 1 is to further characterize the P. falciparum TCTP, building on recent observations that it binds with artemisinin, heme, and calcium. Accordingly they will attempt to determine the subcellular localization of TCTP, and determine the affinity of TCTP for calcium and other ligands. They will attempt to identify where artemisinin forms its covalent bonds in TCTP and determine how artemisinin affects TCTP function. Studies involving comparisons with the human TCTP and with genetically engineered mutant reconbinant TCTPs are also planned.

描述（改编自申请人的摘要）：Meshnick博士和 同事已经确定其中一种青蒿素靶蛋白是 翻译控制的肿瘤蛋白（TCTP）同源物。这个疟原虫 恶性TCTP已克隆并测序，并纯化的重组 已经获得了TCTP。重组TCTP免疫沉淀的抗体 （3H）来自药物治疗的寄生虫的二氢甲蛋白-TCTP复合物。目的 1是为了进一步描述恶性疟原虫TCTP，建立在最近的基础上 观察到它与青蒿素，血红素和钙结合。 因此，他们将尝试确定亚细胞定位 TCTP，并确定TCTP对钙和其他的亲和力 配体。他们将试图确定阿丁蛋白蛋白在哪里形成 TCTP中的共价键，并确定阿霉素如何影响TCTP 功能。涉及与人类TCTP进行比较的研究 还计划了基因工程的突变体侦查TCTP。