Table 1.

Comparing peptidomimetics attributes with native peptides

Characteristics	Peptides	Peptidomimetics	References
Stability	Limited stability toward proteolysis	Higher stability toward proteolysis	Trabocchi (2019), Li Petri et al. (2022), Trabocchi and Guarna (2014)
Interactions/ Specificity	✓ Low selectivity due to high backbone flexibility ✓ Interaction with multiple targets	✓ Higher receptor affinity and selectivity ✓ Pharmacophore-based target selection
Transport system	Rapid excretion, poor cell permeability, lacks specific transport systems due to its relatively high molecular mass	✓ Transports from Peptide transporter 2 (PEPT2) which is a low-capacity/high-affinity proton-coupled cotransporter of diverse di- and tripeptides ✓ The di/tripeptide transporter in the small intestine absorbs some of them
Activity	Limited activity	Higher activity	Kim et al. (2015)
Duration of action	Shorter duration of action	longer duration of action