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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 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.

SUBMITTER: Collins JM

PROVIDER: S-EPMC10710472 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature

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Total wash elimination for solid phase peptide synthesis.

Collins Jonathan M JM Singh Sandeep K SK White Travis A TA Cesta Drew J DJ Simpson Colin L CL Tubb Levi J LJ Houser Christopher L CL

Nature communications 20231209 1

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 ...[more]

PMID: 38071224

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