Methods for Isotope Labelling of Glycans

聚糖的同位素标记方法

• 批准号: 10684319
• 负责人: Maciej Walczak
• 金额: $ 19.16万
• 依托单位: UNIVERSITY OF COLORADO
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-01 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10684319
• 关键词: Address; Aldehydes; Alkylation; Amination; Amines; Area; Benchmarking; Binding; Biochemical; Carbohydrates; Carbon; Carbon Monoxide; Chemicals; Chemistry; Collection; Complement; Complex; Cytolysis; Data; Derivation procedure; Diagnosis; Disaccharides; Disease; Drug Design; Enzymatic Biochemistry; Equilibrium; Glycoconjugates; Glycoproteins; Heparan Sulfate Proteoglycan; Heparin Lyase; Heparitin Sulfate; Human; Human Milk; Interruption; Isotope Labeling; Isotopes; Kinetics; Knowledge; Label; Ligands; Link; Mass Spectrum Analysis; Mediating; Medicine; Metabolic; Methodology; Methods; Modernization; Monosaccharides; Oligosaccharides; Pathologic Processes; Phenotype; Physiological Processes; Play; Polysaccharides; Positioning Attribute; Preparation; Process; Production; Property; Radiolabeled; Reaction; Role; Sampling; Sialic Acids; Source; Structure; Sulfate; System; Techniques; Technology; Therapeutic; Transition Elements; analog; anomer; biological systems; carbohydrate structure; carbonyl group; catalyst; cost; feeding; hydroxyl group; imaging study; in vivo; invention; metabolic engineering; new technology; novel; stable isotope; sugar; technology development; timeline; tool

PROJECT SUMMARY. Glycomics studies are crucial for correlating changes in glycan structure and abundance to the phenotype of a biological system. Among the available platforms to facilitate glycomics analyses, labelling with stable isotopes has been implemented to decipher structural and quantitative aspects of carbohydrates in healthy and diseased states. Isotopically labelled saccharides are also a useful tool for in vivo metabolic profiling and in mechanistic studies in chemistry and enzymology. While some structures are commercially available, a generally applicable and non-destructive method for introducing stable heavy isotopes either in simple monosaccharides or complex oligosaccharides are not available. To overcome these limitations, we will develop a chemical technology based on carbon-13 labelling. To achieve this objective, we will pursue two specific aims: In Aim 1, we will optimize catalytic methods for selective labelling of monosaccharides with carbon-13. This method will selectively exchange the anomeric position with a heavy isotope from readily available sources of carbon-13. In Aim 2, we will apply isotope labelling method to three classes of saccharides of biomedical relevance, namely heparan sulfate proteoglycans, N-linked glycoproteins, and human milk oligosaccharides. Per requirements of PAR-19-254, we will benchmark the new technologies against the current state-of-the-art methods for oligosaccharide quantification. Upon completion of this project, a new catalytic technology for labelling of carbohydrates and glycoconjugates will be available and will complement the current tools for quantitative glycomics. In a broader sense, integration of these novel chemistries with modern mass spectrometry techniques will provide better tools for therapeutic diagnosis.

项目总结。糖组学研究对糖结构和丰度变化的相关性至关重要