Abstract
The 310-helix is a crucial secondary structure in proteins, playing an essential role in various protein–protein interactions, yet stabilizing it in biologically relevant peptides remains challenging. In this study, we investigated the potential of 4-atom hydrocarbon staples to stabilize 310-helices in peptides. Using ring-closing metathesis, we demonstrated that the staple's configuration is critical for both the stabilization and screw sense control of 310-helices. Circular dichroism spectroscopy revealed that the Ri,i+3S(4) staple—a 4-atom cross-link with (R)-configuration at the i position, (S)-configuration at the i + 3 position, and flanked by methyl groups—strongly induces right-handed 310-helices, especially in sequences with proteinogenic L-amino acids. Furthermore, multiple staples effectively stabilized longer peptides, underscoring the versatility of this approach for applications in peptide therapeutics and biomolecular engineering.
Original language | English |
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Article number | 117963 |
Journal | Bioorganic and Medicinal Chemistry |
Volume | 114 |
DOIs | |
State | Published - 15 Nov 2024 |
Keywords
- 3-Helix
- Hydrocarbon staples
- Peptide conformation
- Proteinogenic peptides
- Screw sense control