Jasplakinolides

In contrast, jasplakinolide, a cyclodepsipeptide from the marine sponge Jaspis johnstoni, rapidly penetrates the cell membrane. It competes with phalloidin for F-actin binding and has a dissociation constant of approximately 15 nM. It induces actin polymerization and stabilizes pre-existing actin filaments. Dolastatin 11, a depsipeptide from the mollusk Dolabella auricu-laria, induces F-actin polymerization. Its binding site differs from that of phalloidin or jasplakinolide. 

Dolastatin 10 has been evaluated with promising results in a phase I clinical study in patients with solid tumors. Subsequently, its noticeable antitumor activity was well documented in various in vitro and in vivo tumor models (Madden et al., 2000). More than a dozen dolastatin peptides have been isolated to date. Recent studies have shown, for example, that the depsipeptide dolastatin 11 arrests cells at cytokinesis by causing a rapid and massive rearrangement of the cellular actin filament network and induces the hyperpolymerization of purified actin (Bai et al., 2001). The effects of dolastatin 11 were similar to those of the sponge-derived depsipeptide jasplakinolide however, dolastatin 11 exhibited threefold more cytotoxicity than jasplakinolide in the cells studied. 

Fig. 3.16 Auletta cf. constricta, a brownish sponge that contains jasplakinolide, which is related to jasplakinolides B and C (1023 and 1024)-to make sure which of the two organisms of the picture are addressed (Photo P. Crews)...

Bubb MR, Senderowicz AMJ, Sausville EA, Duncan KLK, Korn ED (1994) Jasplakinolide, a Cytotoxic Natural Product, Induces Actin Polymerization and Competitively Inhibits the Binding of Phalloidin to F-Actin. J Biol Chem 269 14869... 

Senderowicz AMJ, Kaur G, Sainz E, Laing C, Inman WD, Rodriguez J, Crews P, Malspeis L, Grever MR, Sausville EA, Duncan KLK (1995) Jasplakinolide s Inhibition of the Growth of Prostate Carcinoma Cells in Vitro with Disruption of the Actin Cytoskeleton. J Natl Cancer Inst 87 46... 

Tabudravu JN, Morris LA, Milne BF, Jaspars M (2005) Conformational Studies of Free and Li+ Complexed Jasplakinolide, a Cyclic Depsipeptide from the Fijian Marine Sponge... 

From sponges of the genus Jaspis collected at Fiji (300,301), Palau (300), and Papua New Guinea (302), jaspamide (jasplakinolide, 372) was isolated the compound shows potent insecticidal, antifungal, anthelminthic, and ichthyotoxic activity. The structure was determined by X-ray analysis (300). The solution conformation of372 was reported using NMR, molecular mechanics, and dynamics calculations (303). A complexation study was carried out with 372 and the univalent metal ions Li ", Na+, and K+. Li+ binding was observed, and the complex was characterized by NMR and molecular mechanics calculations (304). Jaspamide (372) has potent in... 

One of the key steps in the synthesis of the depsipeptide jasplakinolide involved the preparation of an aldehyde 273 by ozonolysis of an alkene 271 with the correct stereochemistry of the substituents (Scheme 83). The hydroxyl group was protected with R = fer7-butyl(dimethyl)silyl <2004ASC855>. 

Actin Jasplakinolide (Structure 16.1) Sponge, Jaspis sp. Anticancer12... 

Bubb, M. R., Senderowicz, M. J., Sausville, E. A., Duncan, K. L. K., and Korn, E. D., Jasplakinolide, a cytotoxic natural product, induces actin polymerization and competitively inhibits the binding of phalloidin to F-actin, J. Biol. Chem., 269, 14869, 1994. 

A similar enantioconvergent strategy is used for the construction of the hydroxy acid of the biologically active peptides geodiamolide A or jaspamide (jasplakinolide), isolated from lower marine organisms (sponges)442. 

Cramer, L.P. (1999). Role of actin-filament disassembly in lameUipodium protrusion in motile cells revealed using the drug jasplakinolide. Curr. Biol. 9, 1095-1105. 

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