Benzothiazole sulfones as a tool for peptide modification and cleavage

IF 3.5 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Bioorganic & Medicinal Chemistry Pub Date : 2026-02-01 Epub Date: 2025-11-26 DOI:10.1016/j.bmc.2025.118500

Phoebe R. Rubio , Gavin A. Clausen , Zachary D. Ruighaver , Abigail F. Dalton, John P. Blobe, Amanda L. Moore, Christopher R. Shugrue

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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 (S_NAr) 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.

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苯并噻唑砜作为肽修饰和切割的工具。

我们报道了一种新的用于肽修饰和切割的苯并噻唑砜（BTS）工具的开发。苯并噻唑砜是一种亲电试剂，在亲核芳香取代（SNAr）反应中与硫醇迅速反应。通过铜催化叠氮化物-炔环加成（CuAACs），将含炔的BTS化合物结合到含偶氮赖氨酸的肽上。含bts的多肽在室温下可在30分钟或更短时间内与两种等量的巯基亲核试剂快速反应。含bts的肽被偶联到各种不同的化合物上，包括小分子、荧光团和肽。另外，基于bts的可切割连接体也可以用小分子货物（如生物素）合成，并通过CuAAC连接到肽上。这种连接物使固定链霉亲和素的肽捕获和释放成为可能。BTS基序是肽科学中各种应用的通用工具。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Bioorganic & Medicinal Chemistry 医学-生化与分子生物学

CiteScore

6.80

自引率

2.90%

发文量

413

审稿时长

17 days

期刊介绍： Bioorganic & Medicinal Chemistry provides an international forum for the publication of full original research papers and critical reviews on molecular interactions in key biological targets such as receptors, channels, enzymes, nucleotides, lipids and saccharides. The aim of the journal is to promote a better understanding at the molecular level of life processes, and living organisms, as well as the interaction of these with chemical agents. A special feature will be that colour illustrations will be reproduced at no charge to the author, provided that the Editor agrees that colour is essential to the information content of the illustration in question.