ReviewPost screenPeptidomimetic therapeutics: scientific approaches and opportunities

- Naturally occurring peptides are important resources in order to develop pharmaceutical lead compounds.
- Natural peptides are often limited by poor stability or membrane permeability.
- Chemical modifications to peptides can be used to develop enhanced peptidomimetics.
- Peptidomimetics are a promising class of effective, efficient, non-toxic therapeutics.

Natural endogenously occurring peptides exhibit desirable medicinal properties, but are often limited in application by rapid proteolysis and inadequate membrane permeability. However, editing naturally occurring peptide sequences to develop peptidomimetic analogs created a promising class of therapeutics that can augment or inhibit molecular interactions. Here, we discuss a variety of chemical modifications, including l to d isomerization, cyclization, and unnatural amino acid substitution, as well as design strategies, such as attachment to cell-penetrating peptides, which are used to develop peptidomimetics. We also provide examples of approved peptidomimetics and discuss several compounds in clinical trials.