FAQ: University of Utah's Enzymatic Peptide Modification Technology and Sethera Therapeutics
Summary
University of Utah researchers have discovered that the PapB enzyme can create compact rings on therapeutic peptides without the usual leader-sequence requirements, enabling more stable and targeted GLP-1-like therapies. This breakthrough is being commercialized through Utah spinout Sethera Therapeutics to advance next-generation peptide drugs for diabetes and obesity treatment.
What is the main breakthrough described in this research?
The University of Utah team discovered that the radical enzyme PapB can ’tie off’ therapeutic peptides into compact rings without requiring the usual leader-sequence dependencies, enabling programmable modification of GLP-1-like peptides late in drug development.
Why is this enzymatic innovation significant for diabetes and obesity treatment?
This advancement addresses key challenges in peptide stability and tissue-targeting for GLP-1 receptor agonists, allowing researchers to retrofit the same biocatalyst across many sequences with minimal re-engineering while maintaining therapeutic effectiveness.
How does the PapB enzyme work differently from traditional methods?
Unlike classical ribosomally synthesized peptides that require an N-terminal leader sequence, PapB operates leader-independently and can still create thioether rings even when the recognition element domain is deleted or when leader sequences are swapped for unrelated ones.
Who are the key researchers and organizations involved in this development?
The research was led by first author Jacob Pedigo from the Vahe Bandarian Lab in the Department of Chemistry, with commercialization through Sethera Therapeutics co-founded by Vahe Bandarian (CSO) and Karsten A. S. Eastman (CEO), supported by NIH funding.
What are the practical benefits of creating compact C-terminal rings on peptides?
The compact rings can block proteases, stabilize preferred receptor-binding poses, and serve as programmable handles for half-life extension or tissue targeting—all critical features for improving incretin medicines.
Where was this research conducted and published?
The research was conducted at the University of Utah and published in the ACS Bio & Med Chem Au Journal, with patent interests held by the University of Utah and commercialization through Utah-based Sethera Therapeutics.
What makes PapB particularly useful as a research tool?
PapB combines mechanistic specificity with striking substrate promiscuity, working effectively with no native leader, swapped leaders, and non-canonical residues while still producing clean, single-ring products, making it practical for various applications.
How does this technology impact drug development efficiency?
The technology enables researchers to fine-tune approved peptide scaffolds late in development—addressing stability, signaling bias, and tissue targeting—using a single well-behaved enzyme, making the pathway from bench to bedside shorter and more capital-efficient.
What is Sethera Therapeutics’ role in this development?
Sethera Therapeutics is a Utah spinout company co-founded to advance this enzymatic cross-linking technology, using their PolyMacrocyclic Peptide Discovery Platform to revolutionize peptide-based drug development with highly stable, polymacrocyclic peptides.
This story is based on an article that was registered on the blockchain. The original source content used for this article is located at Reportable
Article Control ID: 252246