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Total wash elimination for solid phase peptide synthesis

Author

Listed:
  • Jonathan M. Collins

    (CEM Corporation)

  • Sandeep K. Singh

    (CEM Corporation)

  • Travis A. White

    (CEM Corporation)

  • Drew J. Cesta

    (CEM Corporation)

  • Colin L. Simpson

    (CEM Corporation)

  • Levi J. Tubb

    (CEM Corporation)

  • Christopher L. Houser

    (CEM Corporation)

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.

Suggested Citation

  • Jonathan M. Collins & Sandeep K. Singh & Travis A. White & Drew J. Cesta & Colin L. Simpson & Levi J. Tubb & Christopher L. Houser, 2023. "Total wash elimination for solid phase peptide synthesis," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-44074-5
    DOI: 10.1038/s41467-023-44074-5
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