ChemRxiv
These are preliminary reports that have not been peer-reviewed. They should not be regarded as conclusive, guide clinical practice/health-related behavior, or be reported in news media as established information. For more information, please see our FAQs.
1/1
2 files

De Novo Synthetic Design for Ultrafast Formation of Disulfide Bonds in Peptides and Proteins .pdf

preprint
submitted on 08.10.2020 and posted on 08.10.2020 by Shay Laps, Fatima Atamleh, Guy Kamnesky, Hao Sun, ashraf brik

Despite six decades of efforts to synthesize peptides and proteins bearing multiple disulfide bonds, this synthetic challenge remains an unsolved problem in most targets (e.g. knotted mini proteins). Here we show a de novo general synthetic strategy for the ultrafast, high-yielding formation of two and three disulfide bonds in peptides and proteins. We developed an approach based on the combination of a small molecule, UV-light, and palladium for chemo- and regio-selective activation of Cys, which enables the one-pot formation of multiple disulfide bonds in various peptides and proteins. We prepared bioactive targets of high therapeutic potential, including conotoxin, RANTES, EETI-II, and plectasin peptides and the linaclotide drug. We anticipate that this strategy will be a game-changer in preparing millions of inaccessible targets for drug discovery.

Funding

This project has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (grant agreement no. [831783]).

History

Email Address of Submitting Author

abrik@technion.ac.il

Institution

Technion-Israel Institute of Technology

Country

Israel

ORCID For Submitting Author

0000-0001-8745-2250

Declaration of Conflict of Interest

The authors declare no competing interests.

Exports