Total wash elimination for solid phase peptide synthesis
Abstract We present a process for solid phase peptide synthesis (SPPS) that completely eliminates all solvent intensive washing steps during each amino acid addition cycle. A key breakthrough is the removal of a volatile Fmoc deprotection base through bulk evaporation at elevated temperature while p...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2023-12-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-023-44074-5 |
| _version_ | 1797397892603838464 |
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| author | Jonathan M. Collins Sandeep K. Singh Travis A. White Drew J. Cesta Colin L. Simpson Levi J. Tubb Christopher L. Houser |
| author_facet | Jonathan M. Collins Sandeep K. Singh Travis A. White Drew J. Cesta Colin L. Simpson Levi J. Tubb Christopher L. Houser |
| author_sort | Jonathan M. Collins |
| collection | DOAJ |
| description | Abstract We present a process for solid phase peptide synthesis (SPPS) that completely eliminates all solvent intensive washing steps during each amino acid addition cycle. A key breakthrough is the removal of a volatile Fmoc deprotection base through bulk evaporation at elevated temperature while preventing condensation on the vessel surfaces with a directed headspace gas flushing. This process was demonstrated at both research and production scales without any impact on product quality and when applied to a variety of challenging sequences (up to 89 amino acids in length). The overall result is an extremely fast, high purity, scalable process with a massive waste reduction (up to 95%) while only requiring 10–15% of the standard amount of base used. This transformation of SPPS represents a step-change in peptide manufacturing process efficiency, and should encourage expanded access to peptide-based therapeutics. |
| first_indexed | 2024-03-09T01:16:46Z |
| format | Article |
| id | doaj.art-a55cb64e56434741a270699aa58ecd92 |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-03-09T01:16:46Z |
| publishDate | 2023-12-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-a55cb64e56434741a270699aa58ecd922023-12-10T12:25:12ZengNature PortfolioNature Communications2041-17232023-12-0114111110.1038/s41467-023-44074-5Total wash elimination for solid phase peptide synthesisJonathan M. Collins0Sandeep K. Singh1Travis A. White2Drew J. Cesta3Colin L. Simpson4Levi J. Tubb5Christopher L. Houser6Peptide Synthesis Research, CEM CorporationPeptide Synthesis Research, CEM CorporationPeptide Synthesis Research, CEM CorporationPeptide Synthesis Research, CEM CorporationPeptide Synthesis Research, CEM CorporationPeptide Synthesis Research, CEM CorporationPeptide Synthesis Research, CEM CorporationAbstract We present a process for solid phase peptide synthesis (SPPS) that completely eliminates all solvent intensive washing steps during each amino acid addition cycle. A key breakthrough is the removal of a volatile Fmoc deprotection base through bulk evaporation at elevated temperature while preventing condensation on the vessel surfaces with a directed headspace gas flushing. This process was demonstrated at both research and production scales without any impact on product quality and when applied to a variety of challenging sequences (up to 89 amino acids in length). The overall result is an extremely fast, high purity, scalable process with a massive waste reduction (up to 95%) while only requiring 10–15% of the standard amount of base used. This transformation of SPPS represents a step-change in peptide manufacturing process efficiency, and should encourage expanded access to peptide-based therapeutics.https://doi.org/10.1038/s41467-023-44074-5 |
| spellingShingle | Jonathan M. Collins Sandeep K. Singh Travis A. White Drew J. Cesta Colin L. Simpson Levi J. Tubb Christopher L. Houser Total wash elimination for solid phase peptide synthesis Nature Communications |
| title | Total wash elimination for solid phase peptide synthesis |
| title_full | Total wash elimination for solid phase peptide synthesis |
| title_fullStr | Total wash elimination for solid phase peptide synthesis |
| title_full_unstemmed | Total wash elimination for solid phase peptide synthesis |
| title_short | Total wash elimination for solid phase peptide synthesis |
| title_sort | total wash elimination for solid phase peptide synthesis |
| url | https://doi.org/10.1038/s41467-023-44074-5 |
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