# Development of selective chemical tools to investigate sialyltransferases and sialoside products

> **NIH NIH R21** · SCRIPPS RESEARCH INSTITUTE, THE · 2021 · $208,625

## Abstract

Abstract
Sialylated glycans are widely distributed in mammalian tissues and participate in critical molecular recognition
events that mediate diverse normal biological processes, and pathological processes including infectious
diseases, cancer, autoimmune disease, allergies, Alzheimer’s disease, and many others. In the golgi
apparatus, the 20 known sialyltransferases catalyze the attachment of sialic acid to the penultimate sugar via
three different types of linkages (a2,3-, a2,6-, or a2,8-) to generate a great diversity of sialoglycoconjugates.
The numerous biomedically relevant processes mediated by sialylated glycans are sialic acid linkage
dependent. Thus, tools that can advance our knowledge of sialoglycoconjugate structure and function, and
correlate changes with disease state are of great biomedical interest. Metabolic oligosaccharide engineering
and sialyltransferase inhibition are two powerful approaches to manipulate the expression of cell surface
sialoglycans. However, the current chemical tools used in these strategies are substrates for most
sialyltransferases and therefore report on global sialylation. The goal of this project is to develop novel
chemical tools to address the limitations of these current technologies. In Aim 1 we will develop
sialyltransferase selective chemical tools for metabolic incorporation of sialic acid reporters in a linkage specific
manner. These tools will allow detection, imaging, and purification of sialoglycoconjugates based on sialic acid
linkage. In Aim 2 we will develop sialyltransferase selective inhibitors that will enable the inhibition of specific
sialyltransferases and provide a means to explore the effects of blocking sialylation in a linkage specific
manner. The selective tools will be initially developed by screening against a panel of recombinant human
sialyltransferases then validated in cells. The tools developed in this project will find broad use in biomedical
research as they can be readily adapted to any cellular system and provide more detailed information about
specific sialylation in different disease states.

## Key facts

- **NIH application ID:** 10131222
- **Project number:** 5R21GM135734-02
- **Recipient organization:** SCRIPPS RESEARCH INSTITUTE, THE
- **Principal Investigator:** Corwin Michael Nycholat
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $208,625
- **Award type:** 5
- **Project period:** 2020-04-01 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10131222

## Citation

> US National Institutes of Health, RePORTER application 10131222, Development of selective chemical tools to investigate sialyltransferases and sialoside products (5R21GM135734-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10131222. Licensed CC0.

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