Tunable Linkers for Dynamic Thiol-Based Bioconjugation Strategies
G. Cianfoni, L. Pisano, D. M. Varouhaki, G. Centioni, A. Calcaterra, F. Ghirga, C. M. Athanassopoulos, B. Botta, S. Cammarone, P. Baiocco, D. Quaglio

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.
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,…
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Taxonomy
TopicsClick Chemistry and Applications · Chemical Synthesis and Analysis · Sulfur-Based Synthesis Techniques
