University of Utah research associate Karsten Eastman, along with chemistry Professors Vahe Bandarian and Andrew Roberts, recently collaborated on a study that uncovered a powerful new way to build more stable and drug-like peptides, opening the door to medicines that could target diseases long considered “undruggable”. Published in Proceedings of the National Academy of Sciences (PNAS), their findings are so impactful that Drug Development & Delivery posted an article highlighting the development, titled “Diverse thioether macrocyclized peptides through a radical SAM maturase”.
Currently, many peptide drugs are stabilized with disulfide bonds, which break down in the body, or rely on complicated, costly, and time-consuming chemical methods to achieve the same effect. PapB, a natural enzyme, streamlines the process, creating durable, cyclized peptides that drug developers can program with unprecedented ease. Ultimately, this opens vast new chemical space for peptide medicines, including scaffolds associated with better cell penetration and oral dosing—two qualities essential for advancing peptide therapeutics.
As described in the article featured on Drug Development & Delivery, “the team studied a natural enzyme, called PapB, that can circularize peptides into cyclic structures known as macrocycles. What makes PapB so unusual is that it combines flexibility and precision: it works on many different building blocks—including those that biology usually rejects—yet still creates a single, predictable bond. In one gentle step, it transforms linear peptides into sturdy, ring-shaped molecules that are more stable, resistant to breakdown, and better suited for drug development.” Check out the full paper to learn more about these findings.
Bandarian and Eastman are cofounders of Sethera Theraputics. Dr. Karsten Eastman, serving as CEO, earned his PhD in chemistry from the University of Utah, where he specialized in enzyme and peptide research under the mentorship of Vahe Bandarian, while Bandarian serves as Chief Science Officer. Sethera is revolutionizing peptide-based drug development with their cutting-edge enzymatic cross-linking technology.
Eastman, Roberts, and Bandarian have collaborated on several other publications in the past and will continue to do so. Dr. Karsten Eastman commented: "This project highlights the collaborative strength within the chemistry department at the University of Utah, bringing together organic chemical synthesis from the Roberts group and enzymology from the Bandarian group, leading to the discovery and development of a sequence-agnostic macrocyclization strategy that is immediately useful for chemical biology and has future applications in drug discovery."
The groundbreaking work by Bandarian, Roberts, and Eastman represents a major advance in peptide drug development, offering a simpler, more versatile method to create stable, drug-like molecules. Their discovery not only broadens the potential for targeting previously “undruggable” diseases but also paves the way for more effective, accessible peptide therapeutics. We look forward to seeing their discoveries impact the future of medicine and transform drug development.
9/22/2025
Read the full paper by Andrews, Bandarian, and Eastman in PNAS
Read the article from Drug & Development
Read the article about Sethera from the Research Post
Read more about the research and Sethera in the article from attheU
Learn more about Professors Andrew Roberts and Vahe Bandarian and their research