Structure–Activity Relationships of Anabaenopeptins as Carboxypeptidase and Phosphatase Inhibitors

Anabaenopeptins are a family of cyanobacterial cyclic peptides that display potent enzyme inhibition, particularly against carboxypeptidases A and B, as well as the serine/threonine phosphatases PP1 and PP2A. Defined by a 19-membered macrocyclic ring and a ureido-linked exocyclic amino acid, these compounds vary considerably in their amino acid composition, influencing both potency and selectivity. This review compiles published IC₅₀ values for natural and synthetic anabaenopeptins, organizing them by enzyme target, and highlighting recurring structural motifs that drive inhibitory activity. Through this comparative analysis, we identify emerging trends in structure-activity relationships and underscore gaps in assay standardization and structural validation. These insights provide a critical foundation for advancing the biological evaluation of anabaenopeptins as environmental contaminants, mechanistic probes, and candidate scaffolds for therapeutic development.