Achieving Skeletal Diversity in Peptide Macrocycles through The Use of Heterocyclic Grafts

Despite their therapeutic potential, peptide macrocycles often suffer from drawbacks such as low membrane permeability, proteolytic instability, and conformational lability. As a result, there have been significant efforts to "depeptidize" amino acid-rich macrocycles through the incorporation of heterocyclic grafts into their backbones. In this concept article, we summarize selected recent methodologies that can be used to introduce heterocycles into cyclic peptides.