# Chemical Probes to Study Methionine Redox Biology

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA BERKELEY · 2020 · $383,295

## 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 neurodegenerative and vascular diseases, life span, and cancer progression. To
help decipher contributions of methionine redox physiology and pathology, we are developing new chemical
reagents to selectively label reactive methionine sites in proteins. 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 of methionine oxidation
and reduction. 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 and complementary synthetic, modeling, biochemical, proteomic, and imaging
approaches to provide general tools for probing the reactive methionine landscape. Specifically, we seek to (1)
design and synthesize robust and highly specific oxaziridine probes by establishing a predictive model for
tuning selectivity and stability of methionine adducts, (2) identify oxidatively-sensitive methionine sites and
biochemically characterize specific protein targets involved in reversible redox regulation by chemoproteomic
comparison of cell models with or without the methionine sulfoxide reductase eraser protein on a proteome-
wide scale, and (3) develop new imaging probes based on proximity ligation assays to monitor methionine-
dependent redox status of selected protein targets in cells.

## Key facts

- **NIH application ID:** 10069733
- **Project number:** 1R01GM139245-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA BERKELEY
- **Principal Investigator:** Christopher J. Chang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $383,295
- **Award type:** 1
- **Project period:** 2020-07-15 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10069733

## Citation

> US National Institutes of Health, RePORTER application 10069733, Chemical Probes to Study Methionine Redox Biology (1R01GM139245-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10069733. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*