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Chemical Tools for Protein Glycoengineering

蛋白质糖工程化学工具

基本信息

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
项目类别：
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

项目摘要

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.

总结糖蛋白约占批准用于临床的所有治疗性蛋白质的70 在美国尽管有各种技术可以制造同质材料，即使是最成功的策略也不能只产生一种（少数几种）糖型这种局限性是一个重大挑战，可能会影响疗效、安全性和治疗效果。生产成本。在这个项目中，我们将开发一种广泛适用的技术，消除了与体内和离体糖蛋白产生相关的固有限制系统.在目标1中，我们将发明并优化一种化学生物缀合反应，提供在Asn残基处含有天然聚糖键的糖蛋白作为单个糖型在目标2中，我们将（a）在小分子的多样化中测试新的糖缀合方法，蛋白质和（B）证明其在含有高甘露糖的模型系统中的普遍性聚糖总的来说，新技术将消除安全，监管和知识产权问题目前与糖蛋白生产、操作和表征相关。