Swinholide A, isolated from the marien sponge Theonella swinhoei, is a 44-carbon ring dimeric dilactone macrolide with a 2-fold axis of symmetry. Recent studies have elucidated its unusual structure and shown that it has potent cytotoxic activity. We now report that swinholide A disrupts the actin cytoskeleton of cells grown in culture, sequesters actin dimers in vitro in both polymerizing and non-polymerizing buffers with a binding stoichiometry of one swinholide A molecule per actin dimer, and rapidly severs F-actin in vitro with high cooperativity. These unique properties are sufficient to explain the cytotoxicity of swinholide A. They also suggest that swinholide A might be a model for studies of the mechanism of action of F-actin severing proteins and be therapeutically useful in conditions where filamentous actin contributes to pathologically high viscosities.Applications:• Cell permeable dimeric dilactone macrolide• Cytotoxic compound • Specific actin filament (F-actin) inhibitor. Disrupts the actin cytoskeleton by sequestering actin dimers and rapidly severing actin filaments (F-actin) • Depolymerizes actin filaments (F-actin) • Antifungal • Apoptosis inducer • Alterates the actin cytoskeleton of GH4 cells and inhibits insulin-increased prolactin gene transcriptionAppearance:Supplied as a colorless oilPurity:≥97% (HPLC)Molecular Weight:1389.9Source:Isolated from marine sponge Theonella swinhoeiSolubility:Soluble in ethanol, methanol, DMSO, acetone or ethyl acetate.Storage and Stability:May be stored at 4°C for short-term only. Store at -20°C Stable for 6 months after receipt at -20°C. For maximum recovery of product, centrifuge the original vial after thawing and prior to removing the cap. Further dilutions can be made in assay buffer.
