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Development of Isotopically Labeled Glycoproteins for use as Internal Standards

开发用作内标的同位素标记糖蛋白

基本信息

批准号：
9908593
负责人：
RON ORLANDO
金额：
$ 35.26万
依托单位：
GLYCOSCIENTIFIC, LLC
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-01-01 至 2022-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9908593
关键词：
Amino Acid Sequence Antibodies Biological Products Biological Response Modifier Therapy Cell Line Chinese Hamster Ovary Cell Collection Coupled Development Diagnostic Epoetin Alfa Erythropoietin Fibronectins Funding Glycoproteins Half-Life Human IgG1 IgG2 IgG3 IgG4 Immunoglobulin G Intravenous Immunoglobulins Ions Isotope Labeling Isotopes Laboratories Laboratory Study Legal patent Light Link Malignant Neoplasms Mass Spectrum Analysis Methodology Phase Play Polysaccharides Preparation Procedures Prognostic Marker Proteins Proteome Reagent Recombinant Proteins Recombinants Reference Standards Reproducibility Research Personnel Resources Role Sampling Scheme Scientist Serum Site Structure Therapeutic Therapeutic Agents base cost efficient experimental study glycosylation human monoclonal antibodies improved novel diagnostics overexpression prognostic synthetic biology therapeutic protein virtual

项目摘要

Project Summary/Abstract The ability to accurately quantitate the glycan chains attached to glycoproteins has wide-ranging implications. Numerous studies over the past 40 years have demonstrated that abnormal glycosylation occurs in virtually all types of human cancers, and demonstrates the potential of using glycan markers in either a diagnostic or a prognostic manner. The glycosylation on recombinant protein therapeutics is also known to have profound effects, with one of the better-known examples being the increased serum half-life of erythropoietin (EPO) resulting from glycoengineering. Hence, the quantification of glycoprotein glycans plays important roles from the discovery of new diagnostic/prognostic markers to the development of various therapeutic agents. A current impediment for performing quantitative glycomics is the shortage of widely available standard glycoproteins and isotopically labeled reagents to enable accurate quantitation. The issue with glycan quantitation was highlighted by inter-laboratory studies conducted by the Human Proteome Organization (HUPO) and the Association of Biomolecular Resource Facilities (ABRF). Both of these studies demonstrated errors greater than several hundred percent in the analysis of mid-to-low level glycans were compared across participating laboratories. The inability to accurately quantitate low-level glycans is particularly worrisome since it is often glycans of low abundance that have the greatest impact, as is seen with the therapeutic human intravenous immunoglobulin G (IVIg). The focus of this proposal is to develop a collection of well-characterized standard isotopically labeled glycoproteins to enable the accurate, robust, and reproducible analysis of N- and O-linked glycans at the relative and potentially absolute level. A collection of glycoproteins was selected to cover the needs of both biopharmaceutical and academic researchers. Here, a known quantity of the isotopically labeled glycoprotein can be added directly to the sample, analyzed by any standard procedure that includes mass spectrometry, and glycan quantitation will be provided by comparing the ratios of the native to isotopically labeled ions.

项目总结/文摘