Mammalian Glycosyltransferases for use in Chemistry and Biology

描述（由申请人提供）：复合碳水化合物或聚糖几乎参与每一个生理或病理过程。了解聚糖所起的生物学作用以及影响或改变其功能的因素的进展将为开发新的治疗方法和诊断方法提供重要途径。认识到有机会促进糖科学对人类健康的影响，我们已经组建了一个由五名高级研究人员组成的团队，他们将在三个相关研究项目上合作，利用a Core的独特能力来生产重组哺乳动物糖基转移酶。该研究项目将1)研究糖基转移酶的生化和结构方面，以确定其在分子和结构水平上的受体特异性2)利用新的化学酶方法为糖基转移酶的结构活性关系研究提供聚糖，帮助开发下一代糖基转移酶微阵列和作为分析标准；3)开发经化学报告修饰的糖核苷酸供体来标记糖缀合物亚群，以便在疾病细胞模型中可视化、捕获和鉴定聚糖。三个项目协同效应强。每一种都需要相对较大的糖基转移酶，这些酶将由一个核心产生。此外，它们将产生相互的知识和资源。项目1和项目3将进行互补研究，以揭示糖基转移酶的糖基受体特异性。关于糖基转移酶的糖基受体特异性的信息将被项目2用于制备化学酶合成无法获得的聚糖。项目2将合成聚糖，项目1将利用这些聚糖对糖基受体特异性进行深入研究。项目1的结构研究将为设计用化学报告基因修饰的糖核苷酸供体项目提供重要信息，用于人类疾病的细胞研究。

DESCRIPTION (provided by applicant): Complex carbohydrates or glycans are involved in almost every physiological or pathological process. Advances in understanding the biological roles played by glycans, along with the factors that influence or alter their functions will provid important avenues for the development of new therapeutics, and diagnostics. In recognition of opportunities to advance the impact of glycoscience on human health, we have assembled a team of five senior investigators that will work cooperatively on three related research projects to exploit unique capabilities of a Core to produce recombinant mammalian glycosyltransferases. The research projects will 1) study biochemical and structural aspects of glycosyltransferase to define their acceptor specificities at a molecular and structural level 2) exploit the enzymes in a novel chemoenzymatic approach to provide glycans for structure activity relationship studies, aid in the development of the next generation of glycan microarray and as analytical standards; 3) develop sugar nucleotide donors modified by a chemical reporters to label subsets of glycoconjugates for visualization, capture and identification of glycans in cellular models of disease. The three projects have high synergy. Each requires a relatively large panel of glycosyltransferases that will be produced by a core. In addition, they will generate reciprocal knowledge and resources. Project 1 and 3 will perform complementary studies to uncover glycosyl acceptor specificities of glycosyltransferases. Information about glycosyl acceptor specificities of glycosyltransferases will be employed by Project 2 to prepare glycans that otherwise are not accessible by chemo-enzymatic synthesis. Project 2 will generate synthetic glycans that will be employed by Project 1 for in depth studies of glycosyl acceptor specificities. Structural studies by Project 1 will provide important information for project to design of sugar nucleotide donors modified with a chemical reporter for cellular studies in the context of human disease.