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Dolastatin Peptides

Dolastatin peptides belong to a group of cytotoxic anti-cancer depsipeptides derived from Dolabella auricularia also called the "wedge sea hare" or "Donsol" found in the Indian Ocean, the Western and North West Pacific. Dolabella auricularia belongs to the species of large sea slugs, which is a marine opisthobranch gastropod mollusk in the family aplysiidae, the sea hares. Dolabella auricularia can reach a length of 40 cm. The most important of the dolastatin peptides is dolastatin 10 which is in phase I trials as an anticancer agent. Dolastatin 10 was originally isolated from the sea hare Dolabella auricularia, and was later isolated from the marine cyanobacterium Symploca sp. VP642 from Palau suggesting that the dolastatins and similar peptides maybe metabolic peptides originally present in cyanobacteria. Dolastatin 10 and a chemically related analogue called symplostatin are potent microtubule inhibitor. Dolastatin 11 is a depsipeptide originally isolated from the mollusk Dolabella auricularia. The most potent dolastatins have been reported to be dolastatins 10 and 15. Both of these peptides interact with tubulin and arrest cells in mitosis. Dolastatin 15 has a structure related to Dolastin 10 and is an anti-neoplastic pseudopeptide that inhibits tubulin-dependent GTP hydrolysis to tubulin. Anti-neoplastic drugs or peptides inhibit or prevent the growth and spread of tumors or malignant cells. Dolastatin 15 acts as a weak tubulin inhibitor by binding to the vinca domain of tubulin and induces apoptosis through Bcl-2 phosphorylation in several malignant cell types. This peptide is a potent inhibitor of the proliferation of murine, cancer cell lines and of hematopoietic progenitor cells. When added to leukemia cell cultures dolastatin 15 inhibited both immunoglobulin production and cell proliferation.

Reference
Hendrik Luesch, Richard E. Moore, Valerie J. Paul, Susan L. Mooberry, and Thomas H. Corbett; Isolation of Dolastatin 10 from the Marine Cyanobacterium Symploca Species VP642 and Total Stereochemistry and Biological Evaluation of Its Analogue Symplostatin 1. J. Nat. Prod., 2001, 64 (7), pp 907-910. DOI: 10.1021/np010049y.

David J. Newman and Gordon M. Cragg; Marine Natural Products and Related Compounds in Clinical and Advanced Preclinical Trials. J. Nat. Prod. 2004, 67, 1216-1238.

David J. Newman and Gordon M. Cragg; Marine-Sourced Anti-Cancer and Cancer Pain Control Agents in Clinical and Late Preclinical Development. Mar. Drugs 2014, 12(1), 255-278; doi:10.3390/md12010255 Review.