A critical summary on the discovery of the nineteen members of the phakellistatin family (phakellistatin 1-19), cytotoxic proline-rich cyclopeptides of marine origin, is reported. Isolation, structural elucidation, and biological properties of the various-sized natural macrocycles are described, along with the total syntheses and the enigmatic issues of the cytotoxic activity reproducibility.
Keywords: marine sponge; peptide synthesis; pharmacological activity; proline-rich cyclopeptide.