DOI
10.1016/j.bmc.2025.118500
Abstract
We report the development of a new benzothiazole sulfone (BTS) tool for peptide modification and cleavage. Benzothiazole sulfones are electrophiles that rapidly react with thiols in nucleophilic aromatic substitution (SNAr) reactions. Alkyne-containing BTS compounds were incorporated onto azidolysine-containing peptides through copper-catalyzed azide-alkyne cycloadditions (CuAACs). BTS-containing peptides were found to react rapidly with two equivalents of thiol nucleophiles at room temperature in 30 min or less. BTS-containing peptides were conjugated to a variety of different compounds, including small molecules, fluorophores, and peptides. Alternatively, a BTS-based cleavable linker could also be synthesized with small molecule cargo, such as biotin, and attached to peptides through CuAAC. This linker enabled the capture and release of a peptide with immobilized streptavidin. The BTS motif is a versatile tool for various applications in peptide science.
Document Type
Article
Publication Date
2-2026
Publisher Statement
Copyright © 2026 Elsevier B.V., its licensors, and contributors. All rights are reserved, including those for text and data mining, AI training, and similar technologies. For all open access content, the relevant licensing terms apply.
Recommended Citation
Phoebe R. Rubio, Gavin A. Clausen, Zachary D. Ruighaver, Abigail F. Dalton, John P. Blobe, Amanda L. Moore, Christopher R. Shugrue, Benzothiazole sulfones as a tool for peptide modification and cleavage, Bioorganic & Medicinal Chemistry, Volume 133, 2026, 118500, ISSN 0968-0896, https://doi.org/10.1016/j.bmc.2025.118500.
