Chemical Tools for Protein Glycoengineering

蛋白质糖工程化学工具

• 批准号: 10041583
• 负责人: Maciej Walczak
• 金额: $ 22.77万
• 依托单位: UNIVERSITY OF COLORADO
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-07-01 至 2022-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10041583
• 关键词: Acids; Affect; Amides; Antibodies; Asparagine; Attention; Biological; Biological Models; Cessation of life; Chemicals; Clinical; Coupled; Data; Development; Diagnostic; Esters; Feasibility Studies; Funding; Glycopeptides; Glycoproteins; Goals; Human Resources; Hydrolysis; In Vitro; Link; Literature; Mannose; Methodology; Methods; Modeling; Nature; Oligosaccharides; Peptides; Pharmaceutical Preparations; Polysaccharides; Post-Translational Protein Processing; Production; Protein Engineering; Protein Glycosylation; Proteins; Reaction; Reagent; Recombinant Proteins; Recombinants; Reporting; Safety; Shock; Standardization; System; Technology; Testing; Therapeutic; Training; United States; Vaccines; base; clinical practice; clinically significant; cost; cost effective; crosslink; dehydroalanine; improved; in vivo; interest; new technology; oxidation; racemization; response; small molecule; technology development; technology research and development; therapeutic protein; tool

SUMMARY Glycoproteins constitute approximately 70% of all therapeutic proteins approved for clinical use in the United States. Although there are various technologies available to manufacture homogenous materials, even the most successful strategies fail to produce only one (of a few) glycoform. This limitation represents a major challenge that can affect efficacy, safety, and the costs of production. In this project, we will develop a broadly applicable technology that can eliminate the inherent limitations associated with in vivo and ex vivo glycoprotein production systems. In aim 1, we will invent and optimize a chemical bioconjugation reaction that will furnish glycoproteins containing the native glycan linkage at the Asn residue as a single glycoform. In aim 2, we will (a) test the new glycoconjugation method in diversification of small proteins and (b) demonstrate its generality in a model system containing high-mannose glycans. Taken together, the new technology will eliminate the safety, regulatory, and IP issues currently associated with glycoprotein production, manipulation, and characterization.

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