BPS 2022
Faster time-to-market with Peptide Easy Clean (PEC)
Dominik Sarma
Managing Director, Belyntic GmbH
ABSTRACT
Powerful discovery platforms, including display technologies, venom peptides, and in-silico discovery tools, enable a plethora of peptide hits. However, transforming peptide hits into potent therapeutic leads comes with major manufacturing obstacles. For example, during the early phases of development, the developer requires many pure peptides to confirm the initial hit selection and screen for optimal amino acid substitutions. Moreover, a time-consuming part of selected lead manufacturing is the precipitation step between SPPS and purification. Finally, elaborate chemical peptide modification steps, such as disulfide formation, are required to turn the peptide hits into a decisive pharmacological lead.
These stages toward a clinical drug lead consume a lot of time and resources when relying on conventional purification with chromatography, especially high-pressure liquid chromatography (HPLC). For example, peptide precipitation and lyophilization are mandatory after SPPS before loading the resolubilized sample onto a chromatographic column. Then, HPLC can only purify peptides one by one, and modifications typically complicate the purification step resulting in tedious optimization cycles, loss in yield, and enormous solvent consumption.
The Peptide Easy Clean (PEC) technology is a universal peptide manufacturing tool that significantly improves the speed and efficiency of the entire operation. The catch-and-release approach allows for the parallel purification of peptides in automated liquid handling devices. PEC results in high-quality peptide libraries, enhancing subsequent screening and validation test reliability. A direct TFA cocktail immobilization strategy makes the precipitation step after SPPS redundant, accelerating the workflow significantly while at the same time dispensing solubilization issues for complex peptides. Furthermore, oxidation of the unprotected peptide on-purification resin allows for the efficient and quick late-stage formation of disulfide peptides in a combined purification and modification method.
We highlight PEC in therapeutically relevant case studies. For example, PEC helped manufacture hundreds of epitopes for vaccine research and development. Also, we used PEC for the rapid manufacturing of Solnatide via on-resin disulfide formation. In a third example, we demonstrate the direct TFA cocktail immobilization strategy to synthesize and purify Bivalirudin in a green and fast peptide manufacturing workflow.
BIO
Dominik Sarma did his Ph.D. in the Humboldt-University of Berlin in the field of advanced analytical materials. He founded Belyntic with Robert Zitterbart, Oliver Reimann and Andreas Regnery in 2018. They developed the first universally applicable, cleavable linker for catch-and-release peptide purification and modification. Belyntic marketed several kit products and offers PEC services for custom technology applications. At Belyntic, Dominik is managing director and leads the marketing and quality department.