Affordable sialoglycans and associated reagents for expanded chemoenzymatic production

用于扩大化学酶生产的经济实惠的唾液酸聚糖和相关试剂

基本信息

批准号：
10324760
负责人：
Lim Andrew Lee
金额：
$ 64万
依托单位：
INTEGRATED MICRO-CHROMATOGRAPHY SYSTEMS, INC.
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-09-15 至 2022-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10324760
关键词：
Amines Animals Bacterial Infections Basic Science Binding Proteins Biological Carbon Cell surface Chemicals Collaborations Communities Complex Cytolysis Diagnostic Disaccharides Disease Enzymes Equilibrium Event Family Family member Fermentation Future Glycolipids Glycoproteins Glycosides Goals Homeostasis Human Human Biology Human Milk Human Pathology Human body Hydrophobicity In Situ Industry Infrastructure Malignant Neoplasms Mammals Methods Molecular Probes Monitor Monosaccharides N-Acetylneuraminic Acid N-glycolylneuraminic acid Neoplasm Metastasis Oligosaccharides Pathogenesis Pathologic Processes Physiological Processes Play Polysaccharides Price Process Production Property Protein Engineering Protocols documentation Reaction Reaction Time Reagent Research Role Sales Sialic Acids Specificity Structure System Techniques Testing Therapeutic Vertebral column Virus Diseases base commercialization cost glycosylation glycosyltransferase human disease immunoregulation improved innovation large scale production mannosamine mutant research and development sugar sugar nucleotide therapeutic development

项目摘要

Project Summary Sialoglycans are sialic acid-containing oligosaccharides that play important biological roles in human biology and pathology and are indispensable molecular probes for research related to bacterial and viral infection, cancer metastasis, immune regulation, etc. The multifaceted functions of sialoglycans in human milk are also being explored. Nevertheless, sialoglycan-related research and development of therapeutics and diagnostics have been hampered by the limited access to these structurally complex compounds as well as the high cost and special expertise needed for synthesizing and purifying these reagents. Among various synthetic strategies for producing sialoglycans, glycosyltransferase-based chemoenzymatic methods are attractive strategies. An efficient method for synthesizing structurally defined sialoglycans is one- pot multienzyme (OPME) chemoenzymatic strategy developed by Dr. Hai Yu and Dr. Xi Chen at UC Davis. Each OPME glycosylation reaction contains a glycosyltransferase and enzymes involved in generating the corresponding sugar nucleotide donor in situ from a simple monosaccharide. The OPME reactions allow the synthesis of target glycans containing the desired glycosidic linkage with high regio- and stereo-specificity. At the current stage, large-scale synthesis by the OPME systems is still limited by the scales and the yields of the enzymes produced. In addition, OPME reaction conditions can be improved to decrease the amounts of enzymes used for the synthesis. Product purification processes can also be streamlined using innovative strategies. To advance sialic acid-related research and therapeutic development, the goal of this proposed project is to develop reagents, enzymes, and methods that are ready for commercialization to allow low-cost access to sialoglycans of high demands and their underlying asialoglycans by the broad scientific community (both academic and industry) and to enable highly efficient production of diverse biologically important special sialoglycan targets by even nonspecialists. This will be achieved by the collaboration of the UC Davis team with IMCS which has expertise in high-yield enzyme production by fermentation, unique lysis technique, commercial infrastructure to manufacture, and product sale at affordable prices to the community.

项目摘要唾液聚糖是含有唾液酸的寡糖，在人类生物学和病理学，是与细菌和病毒感染有关的研究的必不可少的分子探针转移，免疫调节等。唾液中乳糖的多面功能也在探索。然而，与缝隙相关的治疗和诊断的研究与开发受到有限的结构复杂化合物以及高成本和高成本和高成本和合成和净化这些试剂所需的特殊专业知识。在产生唾液聚糖的各种合成策略中，基于糖基转移酶的化学酶方法是有吸引力的策略。合成结构定义的唾液聚糖的有效方法是一个 Hai Yu博士和Xi Chen博士在UC Davis开发的Pot Multienzyme（OPME）化学酶策略。每个 OPME糖基化反应包含一种糖基转移酶和参与产生的酶简单的单糖原位原位糖核苷酸供体。 OPME反应允许含有所需的糖苷键具有高区域和立体特异性的靶向糖的合成。在 OPME系统的当前阶段的大规模合成仍然受到尺度和产量的限制产生的酶。另外，可以改善OPME反应条件以减少酶的量用于合成。产品纯化过程也可以使用创新策略来简化。为了促进与唾液酸相关的研究和治疗发展，该拟议项目的目标是开发准备商业化以允许低成本访问的试剂，酶和方法广泛的科学界的高需求及其潜在的Asialogllycans（两者都学术和行业），并能够高效地生产多种生物学上重要的特殊甚至非专业主义者的唾液can目标。加州大学戴维斯（UC Davis）团队的合作将实现这一目标 IMC在发酵，独特的裂解技术，商业方面具有高收益酶的专业知识以负担得起的价格向社区的价格出售基础设施和产品销售。