# Tunable Linkers for Dynamic Thiol-Based Bioconjugation Strategies

## TL;DR

This review discusses recent advances in thiol-based chemical linkers that allow for reversible and controllable connections between biomolecules, useful in biomedical applications.

## Contribution

The paper provides a comprehensive and critical overview of tunable thiol-based linkers for bioconjugation, emphasizing their dynamic and reversible properties.

## Key findings

- Thiol-based linkers like disulfide bonds and photocleavable groups enable controllable and reversible bioconjugation.
- Applications include peptide synthesis, antibody–drug conjugates, and responsive biomaterials.
- The review identifies current limitations and suggests future directions for improving biocompatibility and functionality.

## Abstract

Recent advancements in bioconjugation chemistry have
increasingly
focused on thiol-based strategies, offering reversible and stimuli-responsive
mechanisms, particularly suited for biomedical applications. This
review aims to provide a critical overview of the latest developments
in thiol-containing linkers, such as disulfide bonds and photocleavable
groups, emphasizing their role in enabling controllable and often
reversible conjugation of biomolecules. The review will explore several
applications, including peptide synthesis and peptide-stapling strategies,
antibody–drug conjugates (ADCs), and responsive biomaterials,
categorize key classes of cleavable thiol-based linkers, and analyze
their mechanisms. Covering the literature from the past 15 years,
focusing on innovations until 2024, this review addresses the chemical
foundations and practical implementations of these systems, identifying
current limitations and proposing future directions for designing
selective, biocompatible, and functionally dynamic conjugation platforms.