# Development of Isotopically Labeled Glycoproteins for use as Internal Standards

> **NIH NIH R42** · GLYCOSCIENTIFIC, LLC · 2020 · $352,644

## Abstract

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.

## Key facts

- **NIH application ID:** 9908593
- **Project number:** 2R42GM113666-02
- **Recipient organization:** GLYCOSCIENTIFIC, LLC
- **Principal Investigator:** RON ORLANDO
- **Activity code:** R42 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $352,644
- **Award type:** 2
- **Project period:** 2015-01-01 → 2022-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9908593

## Citation

> US National Institutes of Health, RePORTER application 9908593, Development of Isotopically Labeled Glycoproteins for use as Internal Standards (2R42GM113666-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9908593. Licensed CC0.

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