Natural Glycans for Functional Glycomics

用于功能糖组学的天然聚糖

• 批准号: 10217203
• 负责人: David Fletcher Smith
• 金额: $ 78.02万
• 依托单位: NATGLYCAN, LLC
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-04-01 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10217203
• 关键词: Acetonitriles; Address; Agreement; Aliquot; Animals; Binding Proteins; Biological; Biological Process; Budgets; Catalogs; Cattle; Cells; Chemistry; Clinical Trials; Colostrum; Communities; Complex; Contracts; Development; Disease; Drug Industry; Egg White; Egg Yolk; Equipment; Equipment and supply inventories; Exhibits; Functional disorder; Funding; Future; Glycobiology; Glycoconjugates; Glycolipids; Glycosaminoglycans; Goals; Heparin; High Pressure Liquid Chromatography; Household; Human; Human Milk; Hybrids; Immunoglobulin G; Incubators; Industrialization; Industry; Infant; Infant formula; International; Investments; Isomerism; Kilogram; Laboratories; Letters; Libraries; Link; Mannose; Manufacturer Name; Mission; Monoclonal Antibodies; Mucins; National Institute of General Medical Sciences; Natural Products; Oligosaccharides; Peptide Nucleic Acids; Pharmacologic Substance; Phase; Physiological; Physiology; Play; Polysaccharides; Powder dose form; Preparation; Price; Process; Production; Proteins; Protocols documentation; Quality Control; Reagent; Recombinants; Reproducibility; Research; Research Personnel; Research Support; Role; Sales; Sampling; Societies; Source; Structure; Surface; System; Technology; Time; United States National Institutes of Health; Vendor; Vial device; Water; Work; base; chemical release; commercialization; cost; experience; in vivo; indexing; interest; mannosyl(9)-N-acetylglucosamine2; manufacturing facility; manufacturing process; meetings; method development; milligram; oxidation; quality assurance; synthetic peptide

Natural Glycans for Functional Glycomics Project Summary/ Abstract During the first decade of the 21st century, NIH made significant investments in glycomics. The Consortium for Functional Glycomics (supported by NIGMS 2001-2012) led a major international effort using a microarray of 611 defined glycans to identify the protein-glycan interactions associated with normal physiology and disease (http://www.functionalglycomics.org/CFGparadigms/index.php/Welcome_to_the_CFG_Paradigm_Pages). This 611 glycan library transformed studies on protein-glycan interactions and revealed the importance of defining the human glycome, estimated to be in the range of 10,000 determinants. A microarray comprised of all possible glycans would allow us to detect and define all physiologically relevant glycan binding proteins (GBP), but the CFG library is now only 575 glycans making the production of large quantities of pure, defined glycans for functional studies critical for advancing glycomics; e.g, mgs of pure human milk oligosaccharides (HMO), available since the 1950’s supported research that led to our understanding of the benefits of HMO in breasfed infants, resulting in infant formula manufacturers introducing HMO into their products in 2014, based on clinical trials supporting their efficacy. Mammalian glycans,on the other hand, expressed on the surfaces of all cells, are generally available only in minute quantities; making them as available as HMO to the research community would rapidly advance understanding of their functions in animal cells. This is now possible using our proprietary technology, Oxidative Release of Natural Glycans (ORNG), which chemically releases glycans from glycoconjugates of any natural material using household bleach. NatGlycan, LLC (NGC) was established to provide biologically relevant natural glycans reliably, economically, and in large quantities. In Phase I we demonstrated the feasibility of producing high mannose N-glycans in mg quantities for sale to the glycoscience community for the first time. We believe the economy of scale will support reasonable prices. Sigma-Aldrich sells 20µg of Man9GlcNAc2 for $688, while NGC is selling 5 mg of Man9GlcNAc2-AEAB for $750. In Phase II of this project we will complete a manufacturing facility to produce 100’s of mg (purity >95%) of all high mannose N- glycans and derivatives that will be useful to the glycobiology community. In addition, we plan to launch highly purified N-glycans representing all of the structures expressed on human and recombinant IgG for use as QC standards in mAb manufacturing; currently an unmet need in the pharmaceutical industry. Since ORNG releases all classes of glycans simultaneously from natural products, we will rapidly expand our product offerings. We will purify the major O-glycans that are in great demand, but not currently available at reasonable cost. We anticipate that by the end of Phase II, we will be offering hundreds of N-glycans and O-glycans (purity >95%) and useful derivatives in multi-miligram amounts. Based on significant sales and orders after our initial product catalog launch, we anticipate being able to support our glycan manufacturing costs and increase profit margins as we increase manufacturing scale in the future.

用于功能性糖果的天然聚糖 项目摘要/摘要 在21世纪的前十年中，NIH对糖胶进行了大量投资。财团 功能性糖基因（由Nigms 2001-2012支持）带领了一项主要的国际努力 611定义的聚糖确定与正常生理和疾病相关的蛋白质 - 聚糖相互作用 （http://www.functionalglycomics.org/cfgparadigms/index.php/welcome_to_the_the_cf_paradigm_pages）。这 611聚糖库改变了对蛋白质 - 聚糖相互作用的研究，并揭示了定义的重要性 人类的Glyce估计在10,000个确定词范围内。一个可能完成的微阵列 聚糖将使我们能够检测并定义所有与物理相关的聚糖结合蛋白（GBP），但是 CFG图书馆现在只有575个Glycans，生产大量纯，定义的Glycans 功能研究对于推进甘氨酸至关重要；例如，纯牛奶寡糖（HMO）的MG， 自1950年支持的研究以来，可用 婴儿，导致婴儿配方奶粉制造商在2014年基于临床，将HMO引入其产品 支持其效率的试验。另一方面，在所有细胞表面上表达的哺乳动物聚糖是 通常仅以微量的数量可用；使它们像HMO一样为研究社区提供 快速提高对它们在动物细胞中功能的理解。现在可以使用我们的专有 技术，天然聚糖（ORNG）的氧化释放，从化学上释放了聚糖 使用家庭漂白剂的任何天然材料的糖缀合物。 Natglycan，LLC（NGC）被建立到 可靠，经济和大量提供与生物学相关的天然聚糖。在第一阶段我们 证明了在毫克出售给Glycoscience的Mg量中生产高甘露糖N-聚糖的可行性 第一次社区。我们认为规模的经济将支持合理的价格。 Sigma-Aldrich卖 20µg MAN9GLCNAC2的价格为688美元，而NGC以750美元的价格出售5毫克的Man9GlCNAC2-AEAB。在第二阶段 项目我们将完成制造工厂，以生产所有高甘露糖N-的100毫克（纯度> 95％） 对糖生物学社区有用的聚糖和衍生物。此外，我们计划发射高度 纯化的n-聚糖，代表在人类和重组IgG上用作QC的所有结构 mab制造的标准；目前，制药行业的需求未满足。由于Orng发行 所有类别的聚糖仅从天然产品中，我们将迅速扩展我们的产品。我们将 净化需求量很大但目前尚不合理的O-Glycans。我们期待 到第二阶段结束时，我们将提供数百个N-聚糖和O-Glycans（纯度> 95％）和有用 多米式量中的衍生物。根据我们最初的产品目录后的销售和订单 发布，我们预计将能够支持我们的聚糖制造成本并提高利润率 将来提高制造规模。