GLYCOCONJUGATES OF LEISHMANIA

杜氏利什曼原虫在水解液中存活和繁殖 在其异基因生命周期的整个环境中。寄生虫是如何 避免破坏是未知的。细胞表面大分子，如 作为糖偶联物，很可能在人的生存中起着关键作用 在恶劣环境中的寄生虫和在与 宿主免疫反应。我们发现L.donovani表达了 一种主要的细胞表面糖偶联物，称为脂磷聚糖(LPG)。 根据我们的结果，这个独特的结构 提出了大分子的概念。 在这一赠款期间的未来几年里，我们将重点关注三个方面 有关液化石油气的各方面：(1) 糖偶联物就会完成。的结构。 磷酸七糖核和末端的位置 半乳糖残留量有待阐明。足够的数量 %的液化石油气碎片可以通过化学和酶法获得 消化和这些片段将通过1H-核磁共振和GC- 完成了MS的整体结构。另外，亲水性的形式 释放到培养介质中的液化石油气以及 将对负责其释放的水解酶进行表征。 (2)研究液化石油气的功能。设计了实验 寻求证据证明液化石油气是蛋白质的抑制剂 激酶C，被认为是导致 吞噬细胞中氧化爆发的诱导。此外, 表面液化石油气改变的突变寄生虫将被分析以获得 对其功能的洞察。突变寄生虫的失败 在预期的环境中茁壮成长将是 确定液化石油气的功能。(3)生物合成途径 将对糖偶联物的性质进行研究。重点将是 重点介绍了液化石油气生物合成的两个基本方面：添加 未经酰化的氨基葡萄糖残基对裂解烷基磷脂的作用 和重复的双糖单元的聚合。从这些 通过研究，我们希望对了解液化石油气的作用有所贡献 在利什曼病的发病机制中发挥作用，并提供一种 化疗方案设计的生化原理 利用液化石油气的独特结构。

Leishmania donovani survives and proliferates in hydrolytic environments throughout its digenetic life cycle. How the parasite avoids destruction is unknown. Cell surface macromolecules, such as glycoconjugates, most likely play a key role in the survival of the parasite in hostile environments and in confrontation with host-immune responses. We have found that L. donovani expresses a major cell surface glycoconjugate called lipophosphoglycan (LPG). On the basis of our results, the structure of this unique macromolecule is proposed. In the ensuring years of this grant period, we will focus on three aspects concerning LPG: (1) The entire structure of the glycoconjugate will be completed. The structure of the phosphoheptasaccharide core and the location of the terminal galactose residue remain to be elucidate. Sufficient quantities of LPG fragments can be obtained by both chemical and enzymatic digestions and these fragments will be examined by 1H-NMR and GC- MS to complete the overall structure. Also, the hydrophilic form of LPG that is released into the culture medium as well as the hydrolytic enzyme responsible for its release will be characterize. (2) The function of LPG will be examined. Experiments are designed to pursue evidence that implicates LPG as in inhibitor of protein kinase C, the enzyme that is believed to be responsible for induction of the oxidative burst in phagocytic cells. In addition, mutant parasites with altered surface LPG will be analyzed to gain insights regarding its function. Failure of the mutant parasites to thrive in expected environments would be a major step in determining the function of LPG. (3) The pathway of biosynthesis of the glycoconjugate will be investigated. Emphasis will be focused on two fundamental aspects of LPG biosynthesis: addition of an unactelyated glucosamine residue to the lyso-alkyl-PI lipid and polymerization of the repeating disaccharide units. 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 the unique structure of LPG.