Benzothiazole sulfones as a tool for peptide modification and cleavage

Area of Science:

• Organic Chemistry
• Biochemistry
• Peptide Science

Background:

• Benzothiazole sulfones are electrophilic compounds.
• They react rapidly with thiols via nucleophilic aromatic substitution (S_NAr).
• Peptide modification and cleavage are crucial in biochemical research.

Purpose of the Study:

• To develop a novel benzothiazole sulfone (BTS) tool for peptide modification and cleavage.
• To explore the utility of BTS compounds in bioconjugation and peptide release applications.

Main Methods:

• Incorporation of alkyne-containing BTS compounds onto azidolysine-containing peptides using copper-catalyzed azide-alkyne cycloadditions (CuAACs).
• Reaction of BTS-containing peptides with thiol nucleophiles.
• Synthesis of BTS-based cleavable linkers for peptide conjugation.

Main Results:

• BTS-containing peptides reacted rapidly with thiol nucleophiles (2 equivalents) at room temperature within 30 minutes.
• BTS-modified peptides were successfully conjugated to various molecules, including small molecules, fluorophores, and other peptides.
• A BTS-based cleavable linker facilitated the capture and release of peptides using streptavidin immobilization.

Conclusions:

• Benzothiazole sulfone (BTS) is a versatile motif for peptide modification and conjugation.
• The BTS tool enables efficient peptide modification and the development of cleavable linkers for controlled peptide release.
• This methodology offers broad applications in peptide science and bioconjugation strategies.