The development of methods to determine cell surface glycosylation with the rapid

描述（由申请人提供）：糖组学正迅速成为生物标志物发现的新范例。已知多种疾病如感染和癌症都涉及糖基化的变化。细胞表面上的聚糖对于理解几乎所有的细胞表面相互作用都很重要。它们是药物的关键靶点，并可能产生细胞特异性疗法。此外，本发明还提供了一种方法， 它们也会脱落，并且可以给出与疾病相关的糖基化变化的指示。细胞表面糖基化的研究仍处于起步阶段。大多数研究采用荧光标记的凝集素，提供很少的结构细节。在本提案中，我们将开发技术，通过使用特异性释放它们并以高灵敏度检查它们的方法来研究表面聚糖。在此过程中，我们将开发全面的方法来确定聚糖结构和微观异质性。为了实现这些任务，我们将开发一种用于糖组学分析的高通量方法，该方法将快速鉴定聚糖结构。鉴于聚糖结构的复杂性和异质性，这一目标似乎是不可能的。然而，我们将开发一种以构建的数据库为核心的方法，该数据库将作为模板，描述符包括液相色谱保留时间、准确质量和串联质谱，以识别单个聚糖（或寡糖）结构。该数据库的创建将形成一个综合数据库的核心，使寡糖的常规分析成为可能。快速鉴定方法的发展将极大地推动糖生物学研究。此外，通过液相色谱法分析聚糖将通过允许分析结构异构体从而增加化合物库的丰富度来提供用于生物标志物发现的新方法。

DESCRIPTION (provided by applicant): Glycomics is rapidly emerging as a new paradigm for biomarker discovery. Diseases as diverse as infection and cancer are known to involve changes in glycosylation. Glycans on cell surfaces are important for understanding nearly all cell surface interactions. They are key targets for drugs and may yield cell-specific therapeutics. In addition, they are also shed and can give indications of the changes in glycosylation associated with the disease. The study of glycosylation of cell surfaces is still in its infancy. The majority of the research has employed fluorescently labeled lectins providing few structural details. In this proposal, we will develop techniques to study surface glycans by using methods that release them specifically and examine them with high sensitivity. In the process, we will develop comprehensive methods to determine glycan structures and micoheterogeneity. To achieve these tasks, we will develop a high throughput method for glycomics analysis that will rapidly identify glycan structures. This goal would have seemed impossible given the complexity and the heterogeneity of glycan structures. However, we will develop a method with a constructed database at its core that will serve as template with descriptors including liquid chromatography retention time, accurate mass, and tandem mass spectrometry to identify individual glycan (or oligosaccharide) structures. The creation of this database will form the kernel of a comprehensive database will allow routine analysis of oligosaccharide possible. The development of methods for the rapid identification will significantly advance glycobiology research. Additionally, the analysis of glycans by liquid chromatography will provide a new method for biomarker discovery by allowing the analysis of structural isomers thereby increasing the richness of the compound pool.