Dolastatin 10, a powerful cytostatic peptide derived from a marine animal: Inhibition of tubulin polymerization mediated through the vinca alkaloid binding domain

An elaborate array of structurally-novel and biologically-active cyclic peptides and depsipeptides are found in blue-green algae (cyanobacteria). Several of these compounds possess structures that are similar to those of natural products from marine invertebrates. Most of these cyclic peptides and depsipeptides, such as the microcystins and the lyngbyatoxins, will probably only be useful as biochemical research tools. A few, however, have the potential for development into useful commercial products. For example, cryptophycin-1, a novel inhibitor of microtubule assembly from Nostoc sp GSV 224, shows impressive activity against a broad spectrum of solid tumors implanted in mice, including multidrug-resistant ones, and majusculamide C, a microfilament-depolymerizing agent from Lyngbya majuscula, shows potent fungicidal activity and may have use in the treatment of resistant fungal-induced diseases of domestic plants and agricultural crops.

Cyclic peptides and depsipeptides from cyanobacteria: a review.

Occurrence of secondary metabolites in microalgae (protoctista) is discussed with respect to the phylogenic or taxonomic relationships of organisms. Biosynthetic mechanisms of certain metabolites such as paralytic shellfish poisoning toxins and polyether toxins are also discussed, and genetic aspects of the secondary metabolite production as well.

Wynand J. Van Zyl

Papers

The structure and synthesis of dolastatin 3