Curated News
By: NewsRamp Editorial Staff
August 21, 2025
Sethera's Enzymatic Stapler Revolutionizes Peptide Drug Design
TLDR
- Sethera Therapeutics' enzymatic stapling platform offers a competitive edge by enabling more stable and orally deliverable peptide therapeutics with reduced development complexity.
- Sethera's radical SAM maturase enzyme precisely forms thioether staples on diverse peptide substrates including non-natural building blocks through controlled enzymatic crosslinking.
- This technology advances peptide medicine development, potentially improving treatments for diabetes and other conditions through more effective and accessible therapeutic options.
- Sethera's enzyme acts as a molecular stapler, creating durable peptide structures that defy traditional enzyme mechanisms with remarkable precision and versatility.
Impact - Why it Matters
This breakthrough matters because peptide therapeutics represent a rapidly growing segment of pharmaceutical development, with applications in diabetes treatment (GLP-1 drugs like Ozempic), cancer therapies, metabolic disorders, and numerous other conditions. Traditional peptide drugs often face stability issues, poor oral bioavailability, and complex manufacturing processes. Sethera's technology addresses these fundamental challenges by creating more stable, potentially orally deliverable peptide structures through a simpler enzymatic process. This could lead to more effective treatments with better patient compliance, reduced manufacturing costs, and expanded therapeutic possibilities for conditions that currently lack optimal treatment options. The ability to work with non-natural building blocks also opens entirely new avenues for drug design that weren't previously possible.
Summary
Sethera Therapeutics, in collaboration with the University of Utah's Department of Chemistry, has achieved a significant breakthrough in peptide therapeutics with the publication of their research in the Proceedings of the National Academy of Sciences (PNAS). The paper details their revolutionary enzymatic crosslinking platform that creates durable thioether "staples" to lock peptides into stable, drug-like cyclic structures. This technology demonstrates remarkable versatility by working across a broad range of substrates, including sequences built entirely from non-natural building blocks, thereby expanding accessible chemical space for therapeutic development.
The platform, described by CEO Karsten Eastman as a precise "molecular stapler," defies traditional enzyme models by showing broad substrate scope with pinpoint bond placement. Unlike natural disulfide bonds found in peptides like insulin, Sethera's thioether staples are chemically robust and protease-resistant, significantly improving stability and pharmacological behavior while potentially supporting oral delivery. The technology can reconstruct sophisticated macrocyclic scaffolds in a single enzymatic step, accomplishing what typically requires complex multi-step synthetic chemistry, making it particularly valuable for designing next-generation peptide therapeutics.
Co-founder Vahe Bandarian emphasized how Utah's translational ecosystem and sustained NIH support in fundamental chemistry and enzymology made this discovery possible. The platform's ability to handle diverse sequences while directing exact bond formation positions Sethera to lead innovation in peptide medicines, with applications potentially impacting treatments ranging from GLP-1 analogs to insulin and various natural hormones, opening new possibilities for more effective, stable, and deliverable peptide-based therapies.
Source Statement
This curated news summary relied on content disributed by Reportable. Read the original source here, Sethera's Enzymatic Stapler Revolutionizes Peptide Drug Design
