The potential
This technology offers an entry into economic manufacturing processes for linear peptide drugs and small proteins. The potential of the peptiligase technology however extends far beyond linear peptides and small proteins, to areas such as macrocyles (cyclotides), antibody-drug conjugates and conjugated dual inhibitors. We wish to explore such opportunities with interested customers and clients.


- EnzyTag’s peptide synthesis technology (“CEPS” or “Chemo Enzymatic Peptide Synthesis”) is a solvent-free adjunct to solid-phase synthesis (SPPS).
- CEPS generates significantly higher yields than SPPS (>2x) in the synthesis of long or complex peptides, and can reduce costs associated with peptide synthesis by up to 50%.
- CEPS technology is capable of synthesizing >90% marketed pharmaceutical peptides, is commercially scalable and requires very little capex to implement with existing SPPS equipment and technologies.

- Expressed Protein Ligation (EPL) is an extrapolation of CEPS which uses ligases to selectively and highly efficiently couple a broad variety of peptides and proteins to each other.
- Technology has significant applications in the discovery field by linking all sorts of payloads via a short peptide linker to proteins.
- A key advantage of EPL over existing bioconjugation technologies is that it produces single, monodisperse products for simplified CMC and PK/PD.
Leading references outlining the technology include:
- Toplak et al. – 2016 – Peptiligase, an organic cosolvent stable and cation-independent peptide ligase for efficient chemoenzymatic peptide synthesis and cyclization in water (DOI: 10.1002/adsc.201600017)
- Schmidt et al. – 2017 – Enzyme-mediated ligation technologies for peptides and proteins (DOI: 10.1016/j.cbpa.2017.01.017)
- Schmidt et al. – 2017 – Omniligase-1 a powerful tool for peptide head-to-tail cyclisation (DOI: 10.1002/adsc.201700314)
- Schmidt et al. – 2018 – Design of a substrate-tailored peptiligase variant for the efficient synthesis of thymosin-α 1 (DOI: 10.1039/c7ob02812a)
- Dr. Rodney Lax shares his insights on peptide therapeutics
- Pawlas, Nuijens et al. – 2019 – Sustainable, cost-efficient manufacturing of therapeutic peptides using chemo-enzymatic peptide synthesis (CEPS) (DOI: 10.1039/c9gc03600h).
- Leendert van den Bos is interviewed by Silvana Maini from Teknoscienze Publisher: https://www.youtube.com/watch?
v=qvZUlEEe7Yo&feature=youtu.be