Curated News
By: NewsRamp Editorial Staff
October 14, 2025
Utah Enzyme Breakthrough Revolutionizes Peptide Drug Development
TLDR
- Sethera Therapeutics' enzyme technology provides a competitive edge by enabling late-stage peptide modifications without costly re-engineering, accelerating drug development timelines.
- The PapB enzyme operates leader-independently, using C-terminal thioether macrocyclization to create stable peptide rings without requiring specific recognition sequences or extensive modifications.
- This innovation improves future diabetes and obesity treatments by creating more stable, targeted peptide therapies that could enhance patient outcomes and quality of life.
- University of Utah researchers discovered an enzyme that can tie therapeutic peptides into compact rings like molecular knots, creating more stable drug candidates.
Impact - Why it Matters
This enzymatic innovation addresses critical limitations in peptide-based therapeutics that affect millions of patients worldwide. For people living with diabetes, obesity, and other conditions treated with peptide drugs, this breakthrough could lead to more effective, stable, and targeted medications with fewer side effects. The technology's ability to fine-tune existing peptide scaffolds late in development means approved drugs could be improved without starting from scratch, potentially accelerating the availability of better treatments. As peptide therapeutics represent one of the fastest-growing segments of the pharmaceutical industry, this advancement could impact numerous disease areas beyond metabolic disorders, including cancer, cardiovascular conditions, and neurological disorders. The leader-independent approach also reduces development costs and timelines, making innovative treatments more accessible and affordable for healthcare systems and patients.
Summary
University of Utah researchers have made a groundbreaking discovery in peptide therapeutics, demonstrating that the radical enzyme PapB can create compact rings in therapeutic peptides without the traditional leader-sequence requirements. This innovation, detailed in the prestigious ACS Bio & Med Chem Au Journal, represents a significant advancement in drug development methodology. The research team, led by first author Jacob Pedigo from Professor Vahe Bandarian's chemistry laboratory, found that PapB operates with remarkable substrate promiscuity while maintaining mechanistic specificity, allowing it to forge thioether rings even when leader sequences are removed or replaced with unrelated ones.
The technology is now transitioning from academic research to clinical development through Utah spinout company Sethera Therapeutics, which was co-founded by Bandarian and Karsten A. S. Eastman. This enzymatic approach directly addresses key challenges in next-generation incretin therapies, particularly peptide stability and tissue-targeting limitations that have hampered GLP-1 receptor agonists used for diabetes and obesity treatment. The ability to apply this programmable modification strategy late in drug development without extensive re-engineering represents a major efficiency improvement over traditional methods, potentially shortening the pathway from laboratory discovery to patient treatment.
The implications for patient care are substantial, as the compact C-terminal rings created by PapB can block proteases, stabilize receptor-binding positions, and serve as programmable handles for half-life extension or tissue targeting. Supported by NIH funding and protected by University of Utah patents, this technology exemplifies how federal investment in academic research fuels local economic development and clinical innovation. Sethera Therapeutics' PolyMacrocyclic Peptide Discovery Platform leverages this enzymatic cross-linking technology to create highly stable peptides with unique architectures for diverse therapeutic applications.
Source Statement
This curated news summary relied on content disributed by Reportable. Read the original source here, Utah Enzyme Breakthrough Revolutionizes Peptide Drug Development
