Tubulin is the target for an ever increasing number of structurally unusual peptides and depsipeptides isolated from a wide range of organisms. Since tubulin is the subunit protein of microtubules, the compounds are usually potently toxic to mammalian cells. Without exception, these (depsi)peptides disrupt cellular microtubules and prevent spindle formation. This causes cells to accumulate at the G2/M phase of the cell cycle through inhibition of mitosis. In biochemical assays, the compounds inhibit microtubule assembly from tubulin and suppress microtubule dynamics at low concentrations. Most of the (depsi)peptides inhibit the binding of Catharanthus alkaloids to tubulin in a noncompetitive manner, GTP hydrolysis by tubulin, and nucleotide turnover at the exchangeable GTP site on beta-tubulin. In general, the (depsi)peptides induce the formation of tubulin oligomers of aberrant morphology. In all cases tubulin rings appear to be formed, but these rings differ in diameter, depending on the (depsi)peptide present during their formation.
Published 2002 Wiley Periodicals, Inc.