Recent developments in retro peptides and proteins - an ongoing topochemical exploration

Main-chain peptidomimetics based on peptide-bond reversal and inversion of chirality represent important structural alterations for peptides and proteins, and are highly significant for biotechnology; these modifications have been widely applied: the d-HIV-protease dimer cleaves only all-d substrate; an all-d-hexapeptide opioid is able to produce analgesia following intraperitoneal administration. Antigenicity and immunogenicity can be achieved by metabolically stable antigens such as all-d-and retro-inverso-isomers of natural antigenic peptides. Isomers, including the retroand retro-inversoforms, of hybrid peptides derived from cercropin A and melittin, maintain antimicrobial activity. Therefore, an insight is provided into structure-activity relationships and the rational design of biologically important isomeric peptides.