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Updated: Jun 6, 2025
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Constructing Thioether/Vinyl Sulfide-tethered Helical Peptides Via Photo-induced Thiol-ene/yne Hydrothiolation
Published on: August 1, 2018
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Photochemically-enabled, post-translational production of C-terminal amides.
David Hymel1, Felix Wojcik2, Kim S Halskov2
1Novo Nordisk Research Center Seattle, Inc., Seattle, WA, USA.
Nature Communications
|November 30, 2024
Summary
This study presents a new, scalable method for C-terminal α-amidation of peptides and proteins. The straightforward three-step process enables efficient production of amidated pharmaceuticals for therapeutic development.
Area of Science:
- Chemical Biology
- Medicinal Chemistry
- Biotechnology
Background:
- C-terminal α-amidated peptides are crucial therapeutic targets.
- Current methods for peptide amidation are limited in scalability for lab and manufacturing use.
Purpose of the Study:
- To develop a straightforward and scalable method for C-terminal α-amidation of peptides and proteins.
- To enable the production of amidated pharmaceuticals not viable with existing technologies.
Main Methods:
- A three-step protocol involving cysteine thiol substitution with a photolabel, photoinduced decarboxylative elimination, and enamide cleavage.
- Application of the protocol in a photoflow reactor for semi-recombinant production.
Main Results:
- Achieved gram-scale C-terminal α-amidation of a peptide YY analogue and a GLP-1/amylin co-agonist precursor.
- Demonstrated robust performance of the reaction cascade in flow conditions.
Conclusions:
- The developed protocol offers a scalable solution for producing C-terminal α-amidated peptides and proteins.
- This chemistry has the potential to advance drug leads into development by overcoming manufacturing limitations.
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