Synthetic approaches of naturally and rationally designed peptides and peptidomimetics

Abstract In the last decade, peptides have emerged as important tools for drug discovery, as they combine the advantages of small molecules, such as stability and bioavailability, with those of proteins, such as selectivity and potency. Moreover, advances in chemical synthesis of peptides have allowed for decreased manufacturing costs, making them more attractive from an industrial point of view. In this chapter, we describe synthetic approaches for several bioactive peptide families, such as cyclic peptides, disulfide-rich peptides, cyclodepsipeptides, lantibiotics, and stapled peptides. Peptidomimetics arise from the modulation or chemical modification of peptides, and have the capacity to mimic their biological function with improved pharmacological properties, and thus, they emerge as potential therapeutic agents. Among the most relevant types of peptidomimetics and which are discussed in this chapter are: peptoids, β-peptides, γ-peptides, δ-peptides, oligoureas, azapeptides, α-aminoxy-peptides, sugar-based peptides, α/β-peptides, and polyamides.