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<p>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 (&gt;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.</p>

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Universal peptide synthesis via solid-phase methods fused with chemputation

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年8月8日

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  • Jacopo Zero,
  • Tristan J. Tyler,
  • Leroy Cronin

摘要

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.