Sethera Therapeutics Announces Enzymatic Platform for Advanced Peptide Drug Development
Sethera Therapeutics has published research on an enzymatic platform that creates stable peptide structures, potentially enabling more effective and orally deliverable peptide therapeutics.
Sethera Therapeutics has announced the publication of peer-reviewed results in the Proceedings of the National Academy of Sciences (PNAS) describing a novel enzymatic crosslinking platform that creates durable thioether staples to lock peptides into stable, drug-like cyclic architectures. This technology represents a significant advancement in peptide therapeutics, offering exceptional versatility by working across a broad range of substrates, including sequences built entirely from non-natural building blocks.
The platform, developed in collaboration with researchers from the Department of Chemistry at the University of Utah, defies traditional enzyme models by demonstrating broad substrate scope with precise bond placement. According to Karsten Eastman, PhD, CEO and co-founder of Sethera, the radical-based enzymatic technology acts as a precise molecular stapler, architecting new peptide structures and locking them into stable configurations that mimic drug-like shapes.
Unlike disulfide bonds found in many natural peptides such as insulin, Sethera's thioether staples are chemically robust and protease-resistant, which significantly improves stability and pharmacological behavior. This enhanced stability could potentially support oral delivery of peptide drugs, addressing a major limitation in current peptide therapeutics that typically require injection. The technology enables reconstruction of sophisticated macrocyclic scaffolds in a single enzymatic step, a process that traditionally demands complex multi-step synthetic chemistry.
The platform's ability to accept non-natural building blocks, including D-amino acids, β-amino acids, and N-methyl residues, expands the accessible chemical space for peptide drug design. This versatility allows for the creation of peptides composed entirely of non-natural components, opening new possibilities for drug development. The research demonstrates how sustained support from organizations such as the NIH in fundamental chemistry and enzymology can lead to transformative discoveries with significant societal impact.
This breakthrough comes at a time when peptide therapeutics are gaining increased attention in pharmaceutical development, with drugs like GLP-1 agonists and insulin demonstrating the therapeutic potential of peptide-based medicines. Sethera's platform directly addresses key challenges in peptide drug development, including stability, delivery, and design flexibility, positioning the company to contribute to the next generation of peptide therapeutics that could offer improved efficacy and patient convenience through potential oral administration routes.