# A Tool for synthetic post-translational modifications of cysteines

> **NIH NIH R21** · COLUMBIA UNIV NEW YORK MORNINGSIDE · 2022 · $196,338

## Abstract

Principal Investigator/Program Director (Last, First, Middle): Rovis, Tomislav
A tool for synthetic post-translational modifications of cysteines
Abstract-
 The ability to selectively install amino acid residues within a protein scaffold has been
monumental in deconvoluting the central dogma of biology. Specifically, introducing unnatural
amino acids (UAAs) have aided in the investigation of mechanistic studies within proteins, and
has incentivized the community to develop synthetic methods for installing UAAs. Within this field,
it is valuable to be able to install UAAs that contain post-translational modifications (PTMs),
especially those that are native to biology. In particular, the understanding of protein
phosphorylation is still limited by the lack of mechanistic understanding of phosphorylation
pathways. Therefore, there is an impetus to synthetically incorporate phosphorylated amino acids
into a protein scaffold. We aim to create a method to synthetically install natural PTMs within a
protein scaffold using Cys thiols and photoredox catalysis.
 Herein, we propose a
method to utilize Cys-containing
peptides as a precursor for
carbon-centered radicals, which
can be further functionalized via
nickel catalysis. In this regard, desulfurization can occur through the β-scission of the Cys thiyl
radical and a phosphine, generating a new C-centered radical. By choosing the coupling partner,
a variety of aryl functionality can be incorporated selectively at the Cys position. In addition, aryl
functionality equipped with natural PTMs can be directly incorporated into a protein scaffold.
 The specific goals of this research are as follows:
 1) Develop a site-selective arylation protocol for conversion of cysteine to
phosphotyrosine
 2) Extend this method to Cys modification in oligopeptides and proteins

## Key facts

- **NIH application ID:** 10378706
- **Project number:** 5R21GM141781-02
- **Recipient organization:** COLUMBIA UNIV NEW YORK MORNINGSIDE
- **Principal Investigator:** Tomislav Rovis
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $196,338
- **Award type:** 5
- **Project period:** 2021-04-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10378706

## Citation

> US National Institutes of Health, RePORTER application 10378706, A Tool for synthetic post-translational modifications of cysteines (5R21GM141781-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10378706. Licensed CC0.

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