Work

Merging the Passerini reaction with chemo-enzymatic synthesis for C-terminal peptide modification

Year: 2025

Type: article

Abstract: Over the past few decades, peptide/protein synthesis and bio-conjugation has gained increasing interest in the research community owing to the high demand for strategies that provide modified protein adducts in a site-selective fashion. Herein, we report a novel approach that combines the Passerini multicomponent reaction and chemo-enzymatic peptide synthesis (CEPS) for the selective bio-conjugation of peptide C-termini. The Passerini utilizes aqueous acidic buffer conditions to establish chemoselectivity for the carboxylic acids, while the subsequent enzymatic ligation selectively targets the formed C-terminal substrates. We functionalized a diverse set of pentapeptides utilizing numerous isocyanide and car-bonyl compounds and successfully performed subsequent ligations. This combined multicomponent chemoenzymatic method therefore represents a valuable novel technology for future research into site-selective C-terminal modification of peptides/proteins.

Source: Cell Reports Physical Science

DOI: 10.1016/j.xcrp.2025.102860