Universal peptide synthesis via solid-phase methods fused with chemputation
Abstract Since the advent of automated solid-phase peptide synthesis (SPPS), many commercial platforms have been developed, facilitating cutting-edge research across many biochemical fields. However, despite considerable technological advancements, these systems remain limited in flexibility and che...
Saved in:
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2025-08-01
|
| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-62344-2 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| Summary: | Abstract Since the advent of automated solid-phase peptide synthesis (SPPS), many commercial platforms have been developed, facilitating cutting-edge research across many biochemical fields. However, despite considerable technological advancements, these systems remain limited in flexibility and chemical capability. Herein, we present a fully automated programmable platform that combines the efficiency of SPPS with the chemical flexibility of a Chemical Processing Unit (Chemputer). SPPS protocols, from resin swelling to peptide precipitation, are captured and automated using the Chemical Description Language (χDL), affording peptide sequences in high purity (>79%) and on a multi-milligram scale. Owing to the modularity of the platform, valuable transformations are integrated into the workflow, including ring-closing metathesis, copper-catalyzed azide-alkyne cycloaddition, and native chemical ligation. These tailored modifications are carried out in one, uninterrupted synthetic protocol, performing up to 1635-unit operations, executed over 85 h of activity, producing peptides such as GHRH(1-29), Semaglutide, and Capitellacin, finally unlocking bottlenecks in automated SPPS. |
|---|---|
| ISSN: | 2041-1723 |