PapB enzyme cyclizes drugs, boosting Ozempic stability
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- PapB is a radical SAM enzyme that can macrocyclize GLP‑1-like peptides by forming a thioether bond between their C‑ and N‑termini, creating stable ring structures without needing a leader sequence.
- University of Utah researchers demonstrated that PapB successfully cyclized three different GLP‑1-like peptides, including those containing nonstandard amino acids used in modern incretin drugs.
- Karsten Eastman (co‑author and CEO of Sethera Therapeutics) said the enzyme’s ability to produce cyclic peptides could improve drug stability, half‑life, and target interaction, potentially making existing GLP‑1 drugs like Ozempic more durable.
- Sethera Therapeutics was co‑founded by Eastman and Bandarian to translate the macrocyclization platform into commercial peptide therapeutics, and the work was funded by the National Institutes of Health.
- ACS Bio & Med Chem Au published the study (Jacob K. Pedigo et al., 2025) confirming PapB’s leader‑independent C‑terminal modification and its applicability to complex peptide drugs.
- NIH provided funding that supported the development of the PolyMacrocyclic Peptide (pMCP) Discovery Platform, which earned the university’s Technology Licensing Office’s 2025 Founders of the Year award.
Why it matters: Pharmaceutical companies developing GLP‑1 therapeutics stand to gain longer‑acting, more stable formulations, while patients could benefit from fewer doses and improved efficacy; the enzymatic method also cuts the complexity and cost of late‑stage peptide modification compared with traditional chemistry in the pipeline.
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