Spermatinamine, the first natural product inhibitor of isoprenylcysteine carboxyl methyltransferase, a new cancer target

  • Bioorg Med Chem Lett. 2007 Dec 15;17(24):6860-3. doi: 10.1016/j.bmcl.2007.10.021.
Malcolm S Buchanan  1 ,  Anthony R Carroll ,  Gregory A Fechner ,  Anthony Boyle ,  Moana M Simpson ,  Rama Addepalli ,  Vicky M Avery ,  John N A Hooper ,  Nancy Su ,  Huawei Chen ,  Ronald J Quinn
Affiliations
  • 1. Eskitis Institute, Griffith University, Brisbane, Qld 4111, Australia.
PMID: 17964784 DOI: 10.1016/j.bmcl.2007.10.021
Abstract

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 1D and 2D NMR spectroscopy. Spermatinamine is the first natural product inhibitor of ICMT.

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