“…Among recent advances, backbone modification has emerged as an effective strategy using unnatural residues such as β-amino acids − or oligoureas , to replace a few α-amino acid residues in short-acting bioactive peptides in order to achieve enhanced resistance to proteolytic degradation, more favorable pharmacokinetic (PK) properties, and retain biological activity in vivo. As proteolytically stable peptidomimetics, sulfono-γ-AApeptides (Figure ) exhibit remarkable capability of mimicking the helical domain of proteins and modulating a range of medicinally relevant protein–protein interactions (PPIs). − Indeed, helical sulfono-γ-AApeptides, including left-handed − and right-handed homogeneous sulfono-γ-AApeptides, as well as left-handed and right-handed 1:1 heterogeneous α/sulfono-γ-AApeptides, ,− have been demonstrated as suitable backbones for mimicking the helical domain of bioactive peptides owing to their robust helical folding propensity and close similarity to α-helix; however, the replacement of just a few canonical amino acid residues in the long bioactive peptides with unnatural sulfono-γ-AA residues remains rather underexplored …”