# Hydrochalcogenation Reactions with Noncanonical Amino Acids as a Route to Increase Bioconjugate Valency

## TL;DR

This paper introduces a new chemical method to attach multiple molecules to proteins using noncanonical amino acids, enabling the creation of more complex and functional bioconjugates.

## Contribution

A novel thio-yne bioconjugation method using noncanonical amino acids to create trivalent conjugates with site-specific functionality.

## Key findings

- A thio-yne bioconjugation method was developed using rongalite and noncanonical amino acids.
- The method allows for the creation of trivalent conjugates via a Glaser-Hay reaction followed by hydrochalcogenation.
- The approach demonstrates potential for therapeutic and diagnostic applications through multivalent conjugates.

## Abstract

Bioconjugation represents an efficient and rapid mechanism
to enhance
the already extensive utility of proteins; however, it requires the
development of additional chemistries to prevent undesired reactivity
with nascent biological functionalities. Moreover, the ability to
conjugate multiple partners to increase the conjugate valency further
expands potential applications. Herein, we describe the development
and optimization of a thio-yne bioconjugation using rongalite coupled
with noncanonical amino acids (ncAAs) to afford multivalent conjugates.
The site-specificity of the ncAA partner provides a functional handle
to perform a biological Glaser-Hay reaction that installs the functionality
for a secondary hydrochalcogenation. These trivalent conjugates serve
as a proof-of-concept for the development of potent therapeutic and
diagnostic agents that have vast applicability.