Mitigating Pyroglutamate in Microwave-Assisted SPPS: Side-Reaction Control and Sequence–Structure Influence

About this poster

Pyroglutamate (Pgl) formation is a temperature-driven side reaction that compromises the efficiency of lactam-bridged peptide synthesis under MW-assisted SPPS. Here, IRBM systematically evaluates both process parameters and sequence determinants governing intramolecular Pgl formation. Integration of protocol optimization with CD spectroscopy and residue-scanning identifies the key conformational states enabling N-terminal cyclization. These findings establish a defined structure–reactivity framework and deliver a validated synthetic protocol for constrained peptides and macrocyclic therapeutics.