海洋産抗腫瘍活性環状ペプチドの合成研究

抄録

Lipophilic cyclic peptides from marine invertebrates constitute a growing class of naturally occurring antineoplastic and/or cytotoxic substances. These peptides commonly contain two kinds of unusual amino acids, thiazole and oxazoline amino acids, as their constituents. Our continuing efforts on peptide synthesis using two organophosphorus coupling reagents, diphenyl phosphorazidate (DPPA, (C₆H₅O) ₂P (O) N₃) and diethyl phosphorocyanidate (DEPC, (C₂H₅O) ₂P (O) CN), have achieved the syntheses of dolastatin 3 (the proposed structure), ascidiacyclamide, patellamides A, B, and C, ulithiacyclamide, and ulicyclamide. Cytotoxic activity of all of synthesized cyclic peptides and their derivatives was investigated using L1210 murine leukemia cells in culture. Ulithiacyclamide having the oxazoline and disulfide functions showed marked cytotoxicity, ID₅₀=0.04 μg/ml.