Solid-Phase Peptide Macrocyclization and Multifunctionalization via Dipyrrin Construction

We introduce a new and highly efficient synthetic protocol towards multifunctional fluorescent cyclopeptides by solid-phase peptide macrocyclization via dipyrrin construction, with full scope of proteinogenic amino acids and different ring sizes. Various bicyclic peptides can be created by dipyrrin-based crosslinking and double dipyrrin-ring formation. The embedded dipyrrin can be, respectively, either transformed to fluorescent BODIPY and then utilized as cancer-selective targeted protein imaging probe in vitro , or directly employed as a selective metal sensor in aqueous media. This work furnishes a valuable addition to the peptide macrocyclization toolbox and blueprints the development of multifunctional dipyrrin linkers in cyclopeptides for a wide range of potential bioapplications.