University of Utah PapB Enzyme Performs One-Step Thioether Cyclization of GLP-1-Like Peptides — Cleaner Path to Macrocyclic Drug Candidates
ScienceDaily on April 27 highlighted a University of Utah Department of Chemistry team's discovery — published in ACS Bio & Med Chem Au — that the radical-SAM enzyme PapB can macrocyclize GLP-1-like peptides in one step by forming a thioether bond between a cysteine thiol and the C-terminal carboxylate, even when the C-terminal residue is D-configured, β-amino-acid-derived, or N-methylated. The chemistry compresses what is normally a multi-step late-stage cyclization into a single enzymatic reaction, materially reducing the cost and complexity of producing oral-bioavailable peptide drugs. The work positions PapB as a platform tool for next-generation incretin and macrocyclic peptide programs.