Add time:08/04/2019         Source:sciencedirect.com

Publisher SummaryThis chapter focuses on the latest studies conducted on kedarcidin and maduropeptin, the two 9-membered enediyne containing chromoproteins recently isolated and characterized at Bristol-Myers Squibb. Kedarcidin, neocarzinostatin, and maduropeptin are members of a growing class of enediyne-containing chromoproteins that exhibit dual functionalities: a DNA cleaving chromophore and a stabilizing, selective, protease-like apoprotein. Even though maduropeptin apoprotein shows no homology to the kedarcidin and neocarzinostatin class of proteins, the data suggest that the protein component of the neocarzinostatin, kedarcidin, and maduropeptin may provide a “targeted delivery” of the highly cytotoxic chromophores to the chromatin. This “two-pronged” attack could explain the high potency of these natural products. A more thorough understanding of the substrate specificity of these proteins and their mechanism(s) of proteolytic activity, together with knowledge of the chemistry of their corresponding enediyne chromophores, will provide a useful basis for the design of new generation antitumor agents.

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