ANTINEOPLASTIC AGENTS .337. SYNTHESIS OF DOLASTATIN-10 STRUCTURAL MODIFICATIONS

New structural modifications of the marine shell-less mollusk peptide constituent dolastatin 10 (1) have been synthesized, and evaluated aga inst a variety of cancer cell lines and for their ability to inhibit t ubulin polymerization. A number of useful structure-activity relations hips were uncovered. The most important observation was that the dolap henine unit of dolastatin 10 could be satisfactorily replaced with a p henethylamine. Peptide 11C, designated auristatin PE, was found to exh ibit inhibition of cancer cell growth and tubulin assembly comparable to that of dolastatin 10.