Cleavable and Cysteine-Selective Peptide Stapling Via Bifunctional Aryl Thioethers
Abstract
Stapled peptides exhibit superior drug-likeness over linear analogues, and peptide stapling has become a significant strategy for drug discovery. Herein, we report a cleavable, cysteine-selective peptide stapling approach based on aryl thioether derivatives. This efficient method tolerates diverse reagents and peptide sequences. The stapled peptides retain stable α-helical conformations and exhibit improved chemical and enzymatic stability and enhanced cellular membrane permeability. Notably, the stapling moiety is cleavable by exogenous thiols to release native linear peptides, providing a promising tool for peptide drug development.
Fields of Study & Subjects
Chemical Synthesis and Analysis
Click Chemistry and Applications
Sulfur-Based Synthesis Techniques
Publication details
- Journal / source
- Organic Letters
- Publisher
- American Chemical Society (ACS)
- Volume
- 28
- Issue
- 25
- Pages
- 8211–8216
- Publication date
- 13 June 2026
- Language
- EN