Non-symmetric cysteine stapling in native peptides and proteins
Stapling rigidifies peptides through covalent linkages between amino acids. We introduce 2-chloromethyl-6-cyanopyridine for non-symmetric stapling of N-terminal and internal cysteines. This biocompatible method produces diverse peptide macrocycles with enhanced affinity, stability and inhibitory potency. It is applicable to native peptides and proteins alike, demonstrating potential for peptide drug discovery platforms.
Authors
- Christoph Nitsche
- Sven Ullrich (ORCID: https://orcid.org/0000-0003-4184-7024)
- Douglas J. Lawes (ORCID: https://orcid.org/0000-0003-4182-7218)
- Upamali Somathilake (ORCID: https://orcid.org/0009-0007-7598-5675)
- Bishvanwesha Panda
Institutions
- Australian National University (AU)
Publication Details
- Journal
- Chemical Communications
- Published
- 2024-12-10
- DOI
- https://doi.org/10.1039/d4cc04995k
- Citations
- 3
- Primary Topic
- Chemical Synthesis and Analysis
- Type
- article
- Field-Weighted Citation Impact
- 0.70
Funders
- Alexander von Humboldt-Stiftung
- Australian Research Council