Journal
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
Volume 17, Issue 24, Pages 6860-6863Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmcl.2007.10.021
Keywords
isoprenylcysteine methyltransferase (Icmt); cancer target; natural products; pseudoceratina sp; spermine alkaloid; structure elucidation
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Isoprenylcysteine methyltransferase (Icmt) catalyzes the carboxyl methylation of oncogenic proteins in the final step of a series of post-translational modifications. The inhibition of Icmt provides an attractive and novel anticancer target. A natural product high-throughput screening campaign was conducted to discover inhibitors of Icmt. The Australian marine sponge, Pseudoceratina sp., yielded spermatinamine, a novel alkaloid with a bromotyrosyl-spermine-bromotyrosyl sequence, as the bioactive constituent. Its structure was determined by ID and 2D NMR spectroscopy. Spermatinamine is the first natural product inhibitor of Icmt. (c) 2007 Elsevier Ltd. All rights reserved.
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