Ammosamides

Close Encounters of a Third Kind Ammosamides, Blebbestatin and Myosin... 

Figure 3.16 Structures of the myosin binding natural products ammosamide A, ammosamide B, an IAF ammosamide A probe, and S-blebbestatin.

Using an antibody elicited against the IAF tag, immunoprecipitation studies conducted on cells and lysates treated with the IAF probe identified myosin as a primary target. Interestingly, this protein appeared fluorescent after SDS-PAGE analysis suggesting that a covalent attachment was made between the natural product (or its IAF tag) and the protein. While these effects were not seen in control experiments, myosin was validated as a target of the ammosamides by a combination of in vitro analyses and immunoprecipitation studies. 

Further studies examining the specification of these probes in live cells and tissues indicated that the ammosamides did not only target myosin II within muscle but also suggested affinity to other classes of myosin. These studies show, in addition to synthetic materials such as blebbistatin, natural products are also capable of targeting myosin.206... 

Substituted isatins serve as a feedstock for organic synthesis. Williams used 7-iodoisatin as a substrate in the total synthesis of TMC-95A (29) and B (30). Fennical constructed ammosamides A (31) and B (32) around a 4-... 

Streptomyces sp. (CNR-698) Sediment Bahamas (-1618 m) Ammosamides Cell cycle modulators H ughes et o/., 2009a, 2009b Zurwerra, Wullschleger, and Altmann, 2010... 

Hughes, C.C., MacMillan, J.B., Gaudendo, S.P., Jensen, P.R., and Fenical, W. (2009a) The ammosamides structures of cell cycle modulators from a marine-derived Streptomyces species. Angew. Chem. Int. Ed., 48, 725-727. 

Zurwerra, D., Wullschleger, C.W., and Ahmarm, K.-H. (2010) Treasures from the sea Discovery and total synthesis of ammosamides. Angew. Chem., 49, 6936-6938. 

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