GLYCOCONJUGATES OF LEISHMANIA

杜氏利什曼原虫在水解环境中存活和增殖 在其整个生命周期中的环境。 寄生虫是如何 避免毁灭是未知的。 细胞表面大分子，例如 作为糖缀合物，最有可能发挥关键作用的生存 寄生虫在恶劣的环境中， 宿主免疫反应 我们发现L.多诺万尼表示 一种称为脂磷酸聚糖（LPG）的主要细胞表面糖缀合物。 根据我们的结果，这种独特的结构 高分子提出。 在这一补助期的确保年，我们将重点放在三个 （1）对石油气的整个结构进行了分析。 糖缀合物将完成。 的结构 磷酸七糖核心和末端的位置 半乳糖残基仍有待阐明。 足够数量 LPG片段可以通过化学和酶法获得 将通过1H-NMR和GC对这些片段进行检查。 MS完成整体结构。 此外，亲水形式 释放到培养基中的LPG以及 负责其释放水解酶将被表征。 (2)将检查LPG的功能。 实验设计 寻找证据证明LPG是蛋白质的抑制剂 激酶C，这种酶被认为是负责 诱导吞噬细胞中的氧化爆发。 此外，本发明还提供了一种方法， 将分析具有改变的表面LPG的突变寄生虫，以获得 了解其功能。 变种寄生虫的失败 在预期的环境中茁壮成长将是一个重要的步骤， 确定LPG的功能。 (3)生物合成途径 将研究糖缀合物的性质。 重点将 着重于LPG生物合成的两个基本方面：添加 未乙酰化的葡糖胺残基与溶血-烷基-PI脂质 和重复二糖单元的聚合。 从这些 研究，我们希望有助于了解液化石油气的作用 在利什曼病的发病机制中起作用， 化疗方案设计的生物化学原理 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.