**7.2 Dolastatin 15**

*Dolabella auricularia*, cyanobacteria associated sea hare contained another cytotoxic peptide called as dolastatin 15 (**Figure 8**). It was discovered by the process of bioassays guided fractionation and purified it as a minor fraction of about 6.2 mg from 1600 kg of wet sea hare. It was evident that this compound is well associated with the sea hare from its cyanobacterial diet. Dolastatin 15 is a linear heptadepsipeptide composed of the dolavaline (N,N- dimethyl valine), valine, N-Me-valine, proline (x2), 2-hydroxyisovaleric acid. New Dpy moiety present in this peptide was proposed to be originated biosynthetically from the N-acetyl-phenyalanine methyl ester by intramolecular condensation. This peptide showed specific activity towards the P388 lymphocyte leukemia cell line of the national cancer institute (NCI) [61]. Dolastatin 15 was found to bind in the Vinca alkaloid domain of the tubulin complex, a definitive binding site was not identified. On the other hand, this peptide was shown to weakly bind tubulin with concurrent weak inhibition of crytptophyccin 1 binding, its specific acts are still unclear. Further on going work could determine the molecular mechanism of dolastatin 15 activity, although it has been stopped to enter the preclinical trials due to its general toxicity.
