# Chemical Probes to Characterize the Functional States of O-GlcNAc Transferase

> **NIH NIH R01** · UNIVERSITY OF WISCONSIN-MADISON · 2021 · $69,921

## Abstract

Abstract
 O-GlcNAc transferase (OGT) is an essential mammalian glycosyltransferase that modifies intracellular
proteins with a monosaccharide N-acetylglucosamine, called O-GlcNAcylation. Understanding OGT's
function is critically important because this enzyme regulates numerous biological processes, and many of
them become aberrant in human diseases. However, the precise role of OGT remains largely unclear due
to a number of challenges. These include the fact that OGT glycosylates thousands of proteins without an
apparent sequence motif and the dynamic changes of OGT's catalytic activity and substrate specificity
(termed “functional states”) in response to cellular conditions. Conventional O-GlcNAc detection is not
suitable for direct characterizing the OGT enzyme or understanding its regulatory mechanism in cells. We
have designed a conceptually new chemical probe that generates distinct modifications to report different
functional states of OGT. Here, we propose to implement this probe to characterize the structural features
of OGT that contribute to substrate recognition. In addition, we intend to develop cell-permeable, selective
inhibitors and active site probes to investigate the biological roles of OGT and to profile the molecular
signatures that underlying its dysfunction in cancer. The unique chemical tools established in this research
program will provide innovative approaches and unprecedented insights to dissect the molecular basis
underlying complex OGT biology and may discover new pathways leading to cancer.

## Key facts

- **NIH application ID:** 10425866
- **Project number:** 3R01GM121718-05S1
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **Principal Investigator:** Jiaoyang Jiang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $69,921
- **Award type:** 3
- **Project period:** 2017-08-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10425866

## Citation

> US National Institutes of Health, RePORTER application 10425866, Chemical Probes to Characterize the Functional States of O-GlcNAc Transferase (3R01GM121718-05S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10425866. Licensed CC0.

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