PROTEIN DEGRADATION IN P FALCIPARUM

恶性疟原虫中的蛋白质降解

• 批准号: 3565473
• 负责人: DAVID L VANDER JAGT
• 金额: $ 10.04万
• 依托单位: UNIVERSITY OF NEW MEXICO
• 依托单位国家: 美国
• 财政年份: 1984
• 资助国家: 美国
• 起止时间: 1984-07-01 至 1992-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3565473
• 关键词: Plasmodium falciparum; aminoacid; antibody formation; antimalarial agents; drug design /synthesis /production; enzyme linked immunosorbent assay; enzyme structure; growth /development; hemoglobin; high performance liquid chromatography; host organism interaction; human tissue; immunochemistry; lysosomes; monoclonal antibody; peptidases; proteolysis

The goal of this research project is to elucidate the functions of parasite proteases in the growth and maturation of the malarial parasite Plasmodium falciparum. The goal is related to a long- range objective of developing new antimalarial drugs targeted at parasite proteases, especially proteases involved in parasite-host interactions. The specific aims of this project are 1) to characterize acid and neutral proteases and to determine their roles in the degradation of hemoglobin; 2) to determine there roles of ATP-dependent and ATP-independent non-lysosomal proteolysis in the development of P.falciparum; 3) to elucidate the site of action of chloroquine; 4) to determine the roles of proteases in merozoite-host interactions. The following hypotheses will be tested: 1. Digestion of host cytosol by malarial parasites involves acid proteases in the parasite's food vacuole but also involves non- lysosomal pathways for the degradation of hemoglobin. 2. Chloroquine interferes with the digestion of hemoglobin by diverting hemin from sequestration into malarial pigment. The actual inhibitor of parasite growth is free hemin which inhibits proteolysis. 3. Chloroquine resistance results from mutations which increase the efficiency of sequestration of hemin into malarial pigment. 4. Surface proteases of merozoite-stage parasites are active participants in the process of invasion of erythrocytes by P.falciparum. Parasite proteases will be purified by HPLC procedures and will be characterized Cytochemical and immunocytochemical studies of cellular proteases will be carried out. Proteases will be carried out. Proteases will be isolated from various morphological states of the intraerythrocytic parasite.

本研究项目的目的是阐明 疟原虫生长和成熟过程中的寄生虫蛋白酶 恶性疟原虫 目标是一个长期的- 开发新的抗疟药物的范围目标， 寄生虫蛋白酶，特别是寄生虫-宿主蛋白酶， 交互. 该项目的具体目标是：1）表征酸， 中性蛋白酶，并确定其在降解中的作用 2）确定ATP依赖性和 非ATP依赖性非溶酶体蛋白水解在发育中的作用 阐明氯喹的作用部位; 确定裂殖子宿主中蛋白酶的作用， 交互. 将检验以下假设： 1. 疟原虫对宿主胞浆的消化涉及酸 蛋白酶在寄生虫的食物泡，但也涉及非- 用于血红蛋白降解的溶酶体途径。 2. 氯喹干扰血红蛋白的消化， 将氯化血红素从隔离转化为疟疾色素。 的 寄生虫生长的实际抑制剂是游离氯化血红素，其抑制 蛋白水解 3. 氯喹耐药性是由突变引起的， 氯化血红素螯合成疟疾色素的效率。 4. 裂殖子期寄生虫的表面蛋白酶是活跃的 红细胞侵入过程中的参与者， P.falciparum. 寄生虫蛋白酶将通过HPLC程序纯化，并将 细胞化学和免疫细胞化学研究 将进行细胞蛋白酶的研究。 蛋白酶将被携带 出去 蛋白酶将从各种形态状态中分离出来 红细胞内寄生虫