Bachem publishes White Paper on Peptide Easy Clean extending SPPS method to peptide purification

Bachem AG, the leading CMO in development and manufacture of peptides and oligonucleotides, has published a White Paper showing how the Belyntic-developed Peptide Easy Clean (PEC) catch-and-release platform can revolutionize the purification of peptides.

The White Paper A New Turn In Peptide Purification shows how PEC can extend the benefits of the rapid, orthogonal and efficient SPPS (solid phase peptide synthesis) method for synthesizing peptides to their purification as well.

Revolutionizing peptide purification in parallel

This has considerable implications for peptide production since while SPPS is able to synthesize sets of peptides in parallel, the previous go-to purification method, RP-HPLC, is only a linear process that can impose bottlenecks on peptide development and manufacturing.

The catch-and-release PEC platform, developed by Belyntic GmbH following collaborative research  with Bachem, enables the successful and innovative purification of peptides in parallel, also adopting an orthogonal approach to LC that further facilitates purification of difficult peptides: PEC can specifically removes capped peptide truncations, while the peptide catch step is tolerant of a wide range of conditions, enabling loading in organic solvents that are typically incompatible with conventional LC. Additionally, the linker can facilitate solubilization of aggregation-prone peptides through disruption of secondary structure.

Key steps from linking to release

The White Paper first explains how the PEC platform works, showing the role of a reductively cleavable linker tagged to a peptide, which is introduced as the last amino acid at the free amine at the end of the SPPS.

It then explores the PEC process, through the three key steps of Linker Attachment to N-terminus, Cleavage and Catch Steps, and traceless Release of the purified full-length peptide from the linker via reductive dithiothreitol solution, followed by weak acid hydrolysis.

The paper covers application of PEC in rapid development, showing how purification of a set of 20 peptides of a personalized peptide vaccine was performed within six hours, compared to several days for batch processing via RP-HPLC.

Author

The PEC White Paper is based on the joint work of Belyntic and Dr. Gavin Noble, Research & Development Chemist at Bachem UK (BUK). Dr. Noble played a leading role in the development of the PEC platform. At BUK Dr. Noble’s primary focus is undertaking and coordinating investigations into new production methods for research-grade peptide manufacture, as well as supporting the Synthesis and Purification groups in a troubleshooting capacity.

Dr. Noble has been with Bachem since 2014 and spent three months at Bachem Bubendorf in 2015 as part of a knowledge exchange program, working in R&D as a Project Chemist. Prior to his position at Bachem, he researched peptide-targeted liposome nanoparticles for cancer and antimalarial therapies as a post-doctoral fellow at The University of Notre Dame (USA). He obtained his PhD from The University of Manchester (UK), performing research into protein and enzyme activity at synthetic liposome surfaces. Dr. Noble has published several peer-reviewed articles in high-impact journals, with more than 400 citations.

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