Dominik Sarma
Senior Market Manager, Gyros Protein Technologies
Simplified catch-and-release protocol transforms difficult-to-dissolve peptides into routine purifications
Abstract
Peptide purification remains the primary bottleneck in peptide production, despite significant advances in chemical synthesis technology. While HPLC (High-pressure Liquid Chromatography) continues to dominate, complementary purification methods are urgently needed. We present PEC (PurePep® EasyClean) 2.0, an enhanced catch-and-release purification protocol that eliminates the precipitation step after TFA (trifluoroacetic acid) cleavage from the SPPS (solid-phase peptide synthesis) resin, thereby addressing critical workflow inefficiencies associated with traditional methods, particularly for peptides that are difficult to dissolve.
The original PEC protocol required ether precipitation post-cleavage from the SPPS resin, introducing ether-derived aldehyde and ketone contaminations that interfered with the catch-and-release linker chemistry.[1-2] Additionally, precipitation and redissolution steps presented significant challenges for hydrophobic peptides, resulting in material loss and extended processing times.
Building on novel TFA-stable purification beads and findings by Mthembu et al. [3] demonstrating superior performance of thiol-free cleavage cocktails in suppressing back-alkylation, we developed PEC 2.0. This innovation enables direct purification from the TFA cleavage cocktail, as the absence of thiol scavengers prevents interference with the aldehyde-functionalized purification resin. The protocol leverages the TFA cocktail as an optimal peptide solvent, eliminating dissolution challenges.
Our results demonstrate comparable or superior purities and yields compared to previous protocols, with exceptional performance for hydrophobic peptides. The streamlined workflow reduces processing time and standardizes procedures across diverse peptide sequences.
This novel catch-and-release methodology represents a significant advancement in peptide purification technology. By providing a robust alternative to conventional methods that bridges synthesis and purification workflows without intermediate precipitation, PEC 2.0 addresses longstanding challenges in peptide production. The simplified protocol enables researchers to tackle increasingly complex peptide targets while maintaining high throughput and scalability, ultimately accelerating peptide drug development and research applications.
[1] J. Pept. Sci. 2018, 15, e3136
[2] Chem. Sci. 2021, 12, 2389-2396
[3] Org. Process Res. Dev. 2025, 29, 3, 691–703
Bio
Dominik Sarma is a peptide industry professional with a Ph.D. in organic chemistry from Berlin's Humboldt University. In 2018, he co-founded Belyntic with three partners, developing the Peptide Easy Clean (PEC) technology for peptide purification. As co-CEO and head of communications, Sarma helped secure Belyntic's acquisition by Gyros Protein Technologies in 2022. He then joined Gyros as Senior Market Manager, leading strategic market development for their peptide business since late 2022.