Cyanobacterial peptides as a tour de force in the chemical space of antiparasitic agents

Parasites are scarcely addressed target for antimicrobial peptides despite their big impact in health and global economy. The notion of antimicrobial peptides is frequently associated to the innate immune defense of vertebrates and invertebrate vectors, as the ultimate recipients of the parasite infection. These antiparasite peptides are produced by ribosomal synthesis, with few post-translational modifications, and their diversity come mostly from their amino acid sequence. For many of them permeabilization of the cell membrane of the targeted pathogen is crucial for their microbicidal mechanism. In contrast, cyanobacterial peptides are produced either by ribosomal or non-ribosomal biosynthesis. Quite often, they undergo heavy modifications, such as the inclusion of non-proteinogenic amino acids, lipid acylation, cyclation, Nα-methylation, or heterocyclic rings. Furthermore, the few targets identified for cyanobacterial peptides in parasites are intracellular. Some cyanobacterial antiparasite peptides are active at picomolar concentrations, whereas those from higher eukaryotes usually work in the micromolar range. In all, cyanobacterial peptides are an appealing target to develop new antiparasite therapies and a challenge in the invention of new synthetic methods for peptides. This review aims to provide an updated appraisal of antiparasite cyanobacterial peptides and to establish a side-by -side comparison with those antiparasite peptides from higher eukaryotes.