SYNTHESIS, CONFORMATION AND APPLICATION OF GLYCOPEPTIDES

合成肽可用于研究后处理的效果。 在广泛的生物化学上的翻译修饰， 生物物理学和生物学过程在这个周期的前两个周期中， 格兰特，我们已经开发了新的方法，固相 糖肽的合成，并建立了主要作用 糖基化作用于构象、体外稳定性和 肽骨架的某些生物识别特性。 然而，我们和其他人迄今为止提供的例子是 尺寸和复杂性有限。 在目前的建议中，我们将研究 糖肽在更复杂的系统中。 我们将准备和使用 合成的抗菌糖肽，迄今为止还没有被 可用的有用数量，以充分表征其范围， 活动和行动方式。 病理生物化学过程 由于潜在的N-糖基化可能异常， 蛋白质的糖基化位点也将用 对应于人tau蛋白片段的糖肽， 神经纤维缠结的主要蛋白质成分 老年痴呆症 不同糖基化形式的 粘蛋白的重复单位将作为模型， 糖蛋白片段上的糖长度依赖 单克隆抗体和T细胞的识别将是 表征了 为此，N-末端保护的麦芽三糖-和 麦芽庚糖偶联的丝氨酸和苏氨酸残基将被 化学制备。 这些衍生品也将被用作 中长型含糖辅助性T细胞的构建模块 细胞表位肽模型，以研究 糖肽与主要组织相容性蛋白（MHC）的结合， T细胞受体 最后，一种可能的生物技术用途， 糖肽将使用甘露糖基化T细胞表位进行评估， 其中糖附属物被期望帮助提供 抗原呈递细胞内区室的表位 细胞 上述研究将通过分析 糖肽的二级结构和稳定性，以解决 关于行动方式和持续时间的具体问题，以及 糖长度和异头构型依赖性 构象转变 该补助金的模式和方法 建议可以作为以后研究一套新的 糖肽/糖蛋白功能，并可能打开大门，新的 IDE和应用。

Synthetic peptides can be used to investigate the effect of post- translational modifications on a wide range of biochemical, biophysical and biological processes In the first tow cycles of this grant, we have developed new methodologies for the solid-phase synthesis of glycopeptides and have established the principle effects glycosylation exerts on the conformational, in vitro stability and certain biological recognition properties of the peptide backbone. However, the examples provided by us and others to date are limited in size and complexity. In the current proposal, we will undertake the study of glycopeptides in more complex systems. We will prepare and use synthetic antibacterial glycopeptides, which have hitherto not been available in useful quantities to fully characterize their range of activity and mode of action. Pathobiochemical processes that are due to possible abnormal hyperglycosylation of potential N- glycosylation sites of proteins will also be studies with glycopeptides corresponding to fragments of the human tau protein, the main proteinaceous component of the neurofibrillary tangles of Alzheimer~s disease. Differentially glycosylated versions of the repeat unit of the mucin protein will serve as models of glycoprotein fragments on which the sugar length-dependent recognition of monoclonal antibodies and T-cells will be characterized. To this end, N-terminally protected, maltotriose-and maltoheptose-coupled serine and threonine residues will be chemically prepared. These derivatives will also be used as building blocks for middle-sized and long sugar containing T helper cell epitopic peptide models to study the binding of the glycopeptides to major histocompatibility proteins (MHC) and the T-cell receptor. Finally, a possible biotechnological use of glycopeptides will be assessed using mannosylated T-cell epitopes, in which the sugar appendages are expected to help deliver the epitopes to the intracellular compartments of antigen presenting cells. The above listed studies will be complemented with analysis of the secondary structure and stability of the glycopeptides to address specific questions concerning the mode and duration of action, and the sugar length-and anomeric configuration-dependent conformational transitions. The models and methods of this grant proposal can be used later as prototypes for studying a newer set of glycopeptide/glycoprotein functions, and may open doors to new ides and applications.