# Post-translational activation of the C-terminus of polypeptides for the synthesis of peptide thioesters and peptide thioester surrogates

## TL;DR

This paper introduces new chemical methods to activate the ends of proteins for easier protein synthesis.

## Contribution

The paper presents novel chemical strategies for activating the C-terminus of polypeptides to synthesize peptide thioesters.

## Key findings

- Chemical activation methods are compatible with solvents and reagents that are typically incompatible with biological methods.
- The proposed methods aim to expand the possibilities for chemical protein synthesis.

## Abstract

Semisynthesis using recombinant polypeptides is a powerful approach for the synthesis of proteins having a variety of modifications. Peptide thioesters, of which the peptide C-terminus is activated by a thioester, are utilized for coupling peptide building blocks. Biological methods employing intein have been a center for the C-terminal thioesterification of recombinant polypeptides. Chemical activation has emerged as an alternative methodology for synthesizing peptide thioesters from recombinant polypeptides. Chemical reactions are compatible with various solutions containing organic solvents, chaotropic reagents, or detergents that are generally incompatible with biomolecules such as intein. Despite the potential utility of chemical activation, available methods remain limited. This article introduces the methods for the chemical activation of a peptide C-terminus applied to the chemical synthesis of proteins. By showcasing these methodologies, we aim to accelerate the advancement of new chemical reactions and methodologies and broaden the frontiers for the chemical synthesis of proteins.