Mammalian Glycosyltransferases for use in Chemistry and Biology

用于化学和生物学的哺乳动物糖基转移酶

• 批准号: 8874755
• 负责人: Geert-Jan Boons
• 金额: $ 149.18万
• 依托单位: UNIVERSITY OF GEORGIA
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-24 至 2016-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8874755
• 关键词: Anabolism; Autoimmune Diseases; Biochemical; Biological; Biological Process; Biology; Biomedical Research; Biopolymers; Carbohydrates; Catalysis; Cell Proliferation; Cell model; Cell surface; Cells; Chemicals; Chemistry; Complex; Data; Development; Diagnostic; Disease; Embryonic Development; Enzymes; Fertilization; Future; Generations; Genome; Glycobiology; Glycoconjugates; Glycoproteins; Goals; Health; Human; Hydroxyl Radical; Imagery; Immune response; In Situ; Individual; Inflammation; Knowledge; Label; Life; Link; Lipids; Location; Malignant Neoplasms; Mediator of activation protein; Membrane; Modification; Molecular; Monitor; Monosaccharides; National Research Council; Nucleic Acids; Nutraceutical; Oligosaccharides; Organism; Pathologic Processes; Pathway interactions; Physiological Processes; Play; Polysaccharides; Process; Production; Proteins; Publishing; Recombinants; Relative (related person); Reporter; Reporting; Research Personnel; Research Project Grants; Resources; Role; Signal Transduction; Site; Specificity; Structure; Structure-Activity Relationship; Therapeutic; Tissues; Transcript; United States National Academy of Sciences; Work; base; complex biological systems; design; glycosylation; glycosyltransferase; human disease; macromolecule; next generation; novel; novel therapeutics; pathogen; polypeptide; programs; protein folding; public health relevance; sugar; sugar nucleotide; therapeutic development; trafficking

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.

描述（由申请人提供）：复杂的碳水化合物或聚糖几乎参与了每个生理或病理过程。理解聚糖所扮演的生物学作用的进步以及影响或改变其功能的因素将为开发新的治疗学和诊断提供重要途径。为了认识到促进糖科学对人类健康的影响的机会，我们组建了一个由五名高级研究人员组成的团队，这些团队将合作开展三个相关研究项目，以利用核心的独特能力来生产重组的哺乳动物糖基转移酶。研究项目将1）研究糖基转移酶的生化和结构方面，以在分子和结构级别定义其受体特异性2）在一种新型的化学酶方法中利用酶，以提供聚糖为结构活性关系提供帮助，以帮助结构活性研究，帮助下一代Glycan微型微型货币和分析性销售的酶的发展； 3）开发由化学记者修改的糖核苷酸供体，以标记糖缀合物的子集，以可视化，捕获和鉴定疾病细胞模型中聚糖的鉴定。这三个项目具有很高的协同作用。每个都需要一个相对较大的糖基转移酶，该糖基转移酶将由核心产生。此外，它们将产生相互的知识和资源。项目1和3将进行互补研究，以发现糖基转移酶的糖基受体特异性。项目2将采用有关糖基转移酶的糖基受体特异性的信息，以制备化学酶合成无法获得的聚糖。项目2将产生合成的聚糖，这些聚糖将由项目1用于糖基受体特异性的深度研究。项目1撰写的结构研究将为项目提供重要信息，以设计在人类疾病背景下用化学记者修饰的糖核苷酸供体的​​设计。