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

基本信息

批准号：
8740506
负责人：
Geert-Jan Boons
金额：
$ 148.18万
依托单位：
UNIVERSITY OF GEORGIA
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-09-24 至 2018-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8740506
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

项目摘要

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）：复合碳水化合物或聚糖几乎参与所有生理或病理过程。对聚糖所发挥的生物学作用以及影响或改变其功能的因素的了解的进展将为新疗法和诊断学的开发提供重要途径。为了认识到促进糖科学对人类健康影响的机会，我们组建了一个由五名高级研究人员组成的团队，他们将在三个相关的研究项目上合作，利用核心的独特能力来生产重组哺乳动物糖基转移酶。这些研究项目将 1) 研究糖基转移酶的生化和结构方面，以在分子和结构水平上定义其受体特异性 2) 以新颖的化学酶方法利用酶，为结构活性关系研究提供聚糖，帮助开发下一代生成聚糖微阵列并作为分析标准品； 3) 开发经化学报告基因修饰的糖核苷酸供体，以标记糖复合物的子集，以便在疾病细胞模型中可视化、捕获和识别聚糖。三个项目具有较高的协同效应。每一个都需要由核心产生的一组相对较大的糖基转移酶。此外，他们还将产生互惠的知识和资源。项目 1 和 3 将进行互补研究，以揭示糖基转移酶的糖基受体特异性。项目 2 将利用有关糖基转移酶的糖基受体特异性的信息来制备化学酶合成无法获得的聚糖。项目 2 将生成合成聚糖，项目 1 将使用这些合成聚糖来深入研究糖基受体特异性。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，用于人类疾病背景下的细胞研究。