# A New Chemical Technology for Biological Studies and Therapeutic Applications

> **NIH NIH R21** · UT SOUTHWESTERN MEDICAL CENTER · 2020 · $204,166

## Abstract

Project Summary/Abstract
The overarching goal of this research program is to advance the current technology for biomedical research
and drug development. The focus of this study is to develop Redox-assisted Disulfide Direct Conjugation
(RDDC) as a new bioconjugation technology. Cysteine disulfide is a post-translational modification (PTM) that
plays important structural and functional roles in proteins. However, current methods for cysteine disulfide
conjugation and detection all involve reduction of the disulfides prior to functionalization. Such operation erases
the redox information in the protein and eliminates the possibility of differentiating cysteine disulfides from free
cysteines. There is no method available for targeting cysteine disulfides directly. Through this project, we will
provide a new method for direct functionalization of cysteine disulfides without cross-reacting with free
cysteines or compromising the stability of the targeted proteins. It can also be used to detect novel disulfide
PTMs. More broadly, this method may address the long-standing selectivity issue in protein functionalization
that currently relies on kinetic alkylation or protein engineering despite significant limitations. We will measure
the performance of RDDC and demonstrate its utility by homogenous antibody-drug conjugate (ADC) synthesis.
This project will also lay the foundation for the future development of chemoproteomic probes for new PTM
identification and redox profiling.

## Key facts

- **NIH application ID:** 9954782
- **Project number:** 1R21GM137179-01
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **Principal Investigator:** CHUO CHEN
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $204,166
- **Award type:** 1
- **Project period:** 2020-05-01 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9954782

## Citation

> US National Institutes of Health, RePORTER application 9954782, A New Chemical Technology for Biological Studies and Therapeutic Applications (1R21GM137179-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9954782. Licensed CC0.

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