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Biological roles of proteins are often determined by their post-translational modifications, which result in the introduction of various functionalities such as carbohydrates and lipids. The resulting conjugates play pivotal roles in numerous processes, including immune response, cell adhesion, oncogenesis, and signal transduction. As such, the development of methods for site-selective peptide and protein modifications has been a focus of extensive research.
We have recently developed an approach to site- and stereoselective peptide modification using aziridine-2-carboxylic acid-containing peptides. The unique electrophilic nature of this non-proteinogenic residue allows for site-selective conjugation with thiol nucleophiles in a highly selective aziridine ring opening process. A wide range of thiol nucleophiles have been coupled with Azy-containing peptides, both in solution and on solid support. The strategy presents prospects not only for the convergent preparation of complex mucin-like oligosaccharyl-peptide antigen conjugates for cancer vaccine therapy, but also for the assembly of lipopeptides, affinity-tagged peptides, and non-natural selenopeptide conjugates.
