An Orthogonal Protection Strategy for the Synthesis of Conotoxins Containing Three Disulfide Bonds
Disulfide bonds are crucial for stabilizing bioactive peptides such as conotoxins. We have developed a method for synthesizing conotoxins with three disulfide bonds using Mob, Trt, and Acm protection groups for regionally selective synthesis. This approach enabled the efficient synthesis of peptides with the desired disulfide bond connectivities independent of their sequences. Using our strategy, we synthesized five conotoxins, achieving yields of 20-30%. The results demonstrate the potential of our method for synthesizing complex peptides with multiple disulfide bonds.
Authors
- Lai Yue Chan (ORCID: https://orcid.org/0000-0002-9346-2487)
- Hengyu Zhang
- Tao Jiang (ORCID: https://orcid.org/0000-0003-1908-2926)
- David J. Craik (ORCID: https://orcid.org/0000-0003-0007-6796)
- Wenqing Cai
- Rilei Yu (ORCID: https://orcid.org/0000-0001-6625-2014)
- Huanhuan Zhang (ORCID: https://orcid.org/0000-0002-2255-4261)
Institutions
- Australian Research Council (AU)
- The University of Queensland (AU)
- Qingdao National Laboratory for Marine Science and Technology (CN)
- ARC Centre of Excellence for Innovations in Peptide and Protein Science (AU)
- Shandong Academy of Pharmaceutical Sciences (CN)
- Ocean University of China (CN)
Publication Details
- Journal
- Marine Drugs
- Published
- 2025-04-14
- DOI
- https://doi.org/10.3390/md23040168
- Citations
- 4
- Primary Topic
- Nicotinic Acetylcholine Receptors Study
- Type
- article
- Field-Weighted Citation Impact
- 3.22
Funders
- National Natural Science Foundation of China
- Qingdao National Laboratory for Marine Science and Technology