(552c) Membrane Enhanced Peptide Synthesis (MEPS) – Integrating Organic Solvent Nanofiltration (OSN) into Iterative Chemical Reactions

In the pharmaceutical industry, the high potency and specificity of peptides make them more attractive than traditional small-molecule drugs. The chemical synthesis of peptides involves the repetitive addition of amino acid, in between which the intermediate products have to be isolated for purification purposes. It is of paramount importance to achieve high yield for the isolation of each intermediate product or the cumulative mass loss will be detrimental to overall yield of the synthesis. The conventional peptide synthesis methods, namely Liquid Phase Peptide Synthesis (LPPS) and Solid Phase Peptide Synthesis (SPPS), have been used in the industry over the past few decades, but innovation is still required to improve process performance. Membrane Enhanced Peptide Synthesis (MEPS) integrates Organic Solvent Nanofiltration (OSN) into LPPS. A hexapeptide (Pyr-Ser(Bzl)-Ala-Phe-Asp-Leu-NH2) was synthesised successfully via MEPS at a scale of 33.65 mmol and a soluble anchor concentration of 10.4 wt% in the starting solution. Before the cleavage and global deprotection of peptide, MEPS achieved a high purity (88.1%) and a decent overall yield (71.2%), similar to LPPS (100.0% and 72.4% respectively), in which the intermediate products were precipitated and purified. Consequently, the performance of MEPS was better than LPPS in terms of material cost, process time, volumetric efficiency and E-factor, showing that OSN is indeed a more attractive option than precipitation for the isolation of intermediate products in liquid phase iterative chemical reactions.