# Regulation of Chemical Transformation in Designer Peptide Biomolecular Condensates

## TL;DR

Researchers created designer peptide-based condensates to control chemical reactions, showing how adjusting hydrophobicity affects reaction efficiency and localization.

## Contribution

The study introduces a framework for tuning condensate properties to modulate catalytic reactions using designer peptides.

## Key findings

- Peptide hydrophobicity influences selective partitioning of reactants into condensates.
- Increased hydrophobicity reduces internal diffusion but enhances localized reactivity.
- Condensate dynamics correlate with reaction rates and product formation.

## Abstract

Biomolecular condensates,
formed through liquid–liquid phase
separation, serve as dynamic platforms for biochemical regulation.
Inspired by these natural systems, we develop designer peptide-based
condensates to modulate chemical transformations, focusing on the
Cu­(I)-catalyzed azide–alkyne cycloaddition click reaction between
hydrophobic reactants as a model system. By incorporating a varying
number of isoleucine residues into peptide sequences, we tune the
hydrophobicity of the condensates. This variation allows us to tune
condensate properties, including reactant recruitment, internal mobility,
and catalytic performance. We show that peptide hydrophobicity dictates
selective partitioning of the hydrophobic azide reactant into the
dense phase, while increased hydrophobicity reduces internal diffusion.
Higher molecular mobility within the condensates correlates with increased
reaction rates and product formation, leading to enhanced spatially
localized reactivity within the condensates. Together, our findings
establish a mechanistic framework linking the peptide sequence, condensate
dynamics, and compartmentalized catalysis. This work provides a foundation
for using designer condensates as programmable microreactors for sustainable
chemistry and biomedical applications.