Total wash elimination for solid phase peptide synthesis

Jonathan M. Collins (), Sandeep K. Singh, Travis A. White, Drew J. Cesta, Colin L. Simpson, Levi J. Tubb and Christopher L. Houser
Additional contact information
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

Nature Communications, 2023, vol. 14, issue 1, 1-11

Abstract: 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.

Date: 2023
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DOI: 10.1038/s41467-023-44074-5

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