Peptides containing d -amino acids and retro-inverso peptides

Bioinspired peptides are considered as the most promising alternative for drug design nowadays, acting as anticancer, antiinflammatory, antimicrobial, and delivery agents, as well as inhibitors of amyloidogenesis. However, it is essential to search for efficient and precise strategies to deliver these bioactive molecules into the host system and also to maintain their bioavailability. In this scenario, the design of diastereomeric and all- d -peptides has been applied to increase bioactive peptides’ resistance to endogenous enzymes, as well as their bioavailability. In addition, studies have also proposed the design of d -AMPs organized in the reverse sequence of their parent l -AMPs, known as retro-inverso AMPs, which present high topochemical similarities with their precursors, suggesting equivalent bioactivities. In this context, this chapter will report new advances and obstacles in the engineering of diastereomeric, all- d -enantiomeric and retro-inverso bioactive peptides, with a focus on antimicrobial peptides, mainly highlighting their therapeutic potential.