GLYCOCONJUGATES OF LEISHMANIA

利什曼原虫的糖缀合物

• 批准号: 6169739
• 负责人: Salvatore J Turco
• 金额: $ 30.72万
• 依托单位: UNIVERSITY OF KENTUCKY
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-09-01 至 2003-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6169739
• 关键词: Leishmania donovani; affinity chromatography; carbohydrate biosynthesis; carbohydrate structure; cell membrane; chemical conjugate; enzyme inhibitors; galactose; gas chromatography mass spectrometry; glucosamine; glycolipids; hamsters; high performance liquid chromatography; laboratory mouse; leishmaniasis; leukocyte oxidative burst; lysophospholipids; nuclear magnetic resonance spectroscopy; protein kinase C; protein structure function; species difference

Leishmaniasis is a major health problem to humans and is caused by protozoan parasites of the genus Leishmania. Lipophosphoglycan (LPG) is an important macromolecule on the surface of the promastigote form of these parasites and is believed to be multifunctional. Structurally, LPG is composed of four domains: (i) a lyso-l-O-alkylphosphatidylinositol anchor, (ii) a phosphosaccharide core, (iii) a polymer of repeating saccharide units linked together by phosphodiester bridges, and (iv) a small, capping oligosaccharide at the terminal, non-reducing end. The lipid anchor and phosphosaccharide core regions of LPG are conserved among various Leishmania species, whereas there is variability of sugar composition and sequence in the repeating phosphorylated saccharide units and the capping structure. While significant progress has been made on structure-function relationships of LPG, much more remains to be learned concerning interspecies differences, and intraspecies developmental modifications of LPG structure. Determining these structural differences along with the biosynthesis and turnover of this important glycoconjugate will also be a focus of our research. The specific aims of this application are as follows: l. Continuation of structural analysis of LPGs. Specifically, the structure of LPG from Indian isolates of L. donovani and from isolates of L. braziliensis and L. amazonensis will be elucidated. 2. Biochemical analysis of LPG biosynthesis. Two key enzymes (mannosylphosphate transferase and arabinosyltransferase) involved in LPG biosynthesis will be purified and characterized. 3. Characterization of LPG turnover. The turnover of LPG by the parasite and the fate of LPG upon infection of macrophages by promastigotes will be investigated. From these studies, we hope to contribute to the understanding of the role LPG plays in the pathogenesis of leishmaniasis and to provide a biochemical rationale for the design of chemotherapeutic regimens that exploit its unique structure.

利什曼病是人类的一个主要健康问题，由以下原因引起： 利什曼原虫属原生动物寄生虫。 脂磷酸聚糖 (LPG) 是 前鞭毛体表面的重要大分子 这些寄生虫被认为是多功能的。 从结构上看，液化石油气 由四个结构域组成： (i) 溶血-1-O-烷基磷脂酰肌醇 锚，(ii) 磷酸糖核心，(iii) 重复聚合物 通过磷酸二酯桥连接在一起的糖单元，和(iv) 末端有小的加帽寡糖，非还原端。 这 LPG 的脂质锚和磷酸糖核心区域在 不同的利什曼原虫种类，而糖的含量存在差异 重复磷酸化糖单元的组成和序列 和封盖结构。 虽然已经取得了重大进展 LPG的结构-功能关系，还有很多东西有待了解 关于种间差异和种内发育 液化石油气结构的修改。 确定这些结构差异 随着这种重要糖复合物的生物合成和周转 也将是我们研究的重点。 本次活动的具体目标 申请如下： 湖继续进行液化石油气的结构分析。 具体来说， L. donovani 印度分离株和 L. donovani 分离株的 LPG 结构 将阐明巴西乳杆菌和亚马逊乳杆菌。 2. LPG生物合成的生化分析。 两种关键酶 （甘露糖基磷酸转移酶和阿拉伯糖基转移酶）参与 LPG 生物合成将被纯化和表征。 3. 液化石油气周转量的表征。 寄生虫对液化石油气的周转 前鞭毛体感染巨噬细胞后LPG的命运将是 调查了。 我们希望通过这些研究有助于理解这个角色 液化石油气在利什曼病的发病机制中发挥作用，并提供 设计化疗方案的生化原理 利用其独特的结构。