# Site-Selective Protein Modification via Peptide-Directed Proximity Catalysis

## TL;DR

Researchers developed a method to modify specific sites on proteins using peptides with built-in catalysts, allowing for precise chemical changes.

## Contribution

The introduction of catalyst-functionalized peptides enables site-selective protein modification through proximity catalysis.

## Key findings

- Peptides with pyridinium oxime catalysts can modify proteins with N-acyl-N-alkylsulfonamide reagents.
- Changing the position of the catalyst in the peptide alters the modification site on the protein.
- This approach allows for the development of peptide libraries tailored to specific target proteins.

## Abstract

Proximity catalysis
exploits ligand binding for localized, catalytic
protein modification. In this work, we introduce catalyst-functionalized
peptides as versatile ligands for this approach. Through the functionalization
of target-binding peptides with pyridinium oxime catalysts, we show
that model proteins can be site-selectively modified with a variety
of N-acyl-N-alkylsulfonamide reagents
to introduce common functionalities, including fluorophores and affinity
handles to the protein surface. Critically, we show that simple changes
to the peptide-catalyst structure, moving the pyridinium oxime from
the N- to C-terminus, alter the site of modification. This opens up
possibilities to develop peptide libraries for a particular target
protein and subsequently tuning the modification site for a given
application.