# Chemical Probes to Study Methionine Redox Biology

> **NIH NIH R01** · PRINCETON UNIVERSITY · 2024 · $439,110

## Abstract

Project Summary/Abstract
Protein methionine residues are emerging as essential redox sites for physiological processes spanning signal
transduction, antioxidant defense, and regulation of protein function. At the same time, aberrant elevations in
methionine oxidation induced by oxidative stress and/or inactivation of methionine sulfoxide reductase
enzymes can contribute to cancer, neurodegenerative and vascular diseases, and life span. To decipher
contributions of methionine redox physiology and pathology, we are developing new chemical reagents to
selectively label reactive methionine sites from proteins to proteomes. The scientific premise is that providing
access to a modular chemical toolbox for methionine bioconjugation will help unveil new functional methionine
sites in proteins to further understanding of physiological and pathological contributions through covalent
methionine tagging. Selective methionine bioconjugation using redox-based probes that emulate the innate
oxidative chemistry of these residues offers chemical innovation, while demonstrating scientific rigor through
the combined use of diverse synthetic, modeling, proteomic, and biochemical approaches to provide general
tools for probing the reactive methionine landscape. Specifically, we seek to (1) design robust and highly
specific oxaziridine probes by establishing a predictive model for tuning selectivity and stability of methionine
adducts, (2) identify proteome-wide oxidatively-sensitive methionine sites and analyze motifs to reveal
principles of methionine hyperreactivity, and (3) biochemically characterize targets involved in reversible redox
regulation, with a particular focus on cancer-dependent targets where methionine oxidation can influence
cellular metabolism.

## Key facts

- **NIH application ID:** 11126160
- **Project number:** 7R01GM139245-06
- **Recipient organization:** PRINCETON UNIVERSITY
- **Principal Investigator:** Christopher J. Chang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $439,110
- **Award type:** 7
- **Project period:** 2020-07-15 → 2028-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11126160

## Citation

> US National Institutes of Health, RePORTER application 11126160, Chemical Probes to Study Methionine Redox Biology (7R01GM139245-06). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/11126160. Licensed CC0.

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