Related Experiment Video
Updated: Oct 6, 2025
11:09
Constructing Thioether/Vinyl Sulfide-tethered Helical Peptides Via Photo-induced Thiol-ene/yne Hydrothiolation
Published on: August 1, 2018
10.9K
Peptide stapling by late-stage Suzuki-Miyaura cross-coupling
Hendrik Gruß1, Rebecca C Feiner2, Ridhiwan Mseya3
1Department of Chemistry, Bielefeld University, Universitätsstr. 25, 33615 Bielefeld, Germany.
Beilstein Journal of Organic Chemistry
|January 20, 2022
Summary
Researchers developed a novel peptide stapling method using macrocyclization. This technique enhances alpha-helicity and binding affinity for protein-protein interaction modulators, improving drug design for previously undruggable targets.
Area of Science:
- Medicinal Chemistry
- Structural Biology
- Drug Discovery
Background:
- Peptide stapling stabilizes alpha-helical structures, enabling modulation of protein-protein interactions.
- Previously, targeting these interactions was challenging due to their transient nature and lack of deep binding pockets.
Purpose of the Study:
- To develop a novel peptide stapling technique for creating modulators of protein-protein interactions.
- To optimize linker length for improved peptide rigidity and flexibility.
Main Methods:
- Utilized late-stage Suzuki-Miyaura cross-coupling for macrocyclization.
- Incorporated bromotryptophan into peptides from the axin catenin-binding domain.
- Optimized linker length to balance rigidity and flexibility.
Main Results:
- Achieved enhanced alpha-helicity and increased binding affinity to beta-catenin.
- Demonstrated improved proteolytic stability against proteinase K.
- Successfully designed a novel stapled peptide modulator.
Conclusions:
- The novel macrocyclization approach is effective for peptide stapling.
- Optimized stapled peptides show potential as modulators of protein-protein interactions.
- This method advances the development of therapeutics for previously undruggable targets.
