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Spermatinamine, the first natural product inhibitor of isoprenylcysteine carboxyl methyltransferase, a new cancer target |
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| Authors: | Buchanan Malcolm S Carroll Anthony R Fechner Gregory A Boyle Anthony Simpson Moana M Addepalli Rama Avery Vicky M Hooper John N A Su Nancy Chen Huawei Quinn Ronald J |
| Affiliation: | aEskitis Institute, Griffith University, Brisbane, Qld 4111, Australia bQueensland Centre for Biodiversity, Queensland Museum, South Brisbane, Qld 4101, Australia cAstraZeneca R&D Boston, 35 Gatehouse Drive, Waltham, MA 02451, USA |
| 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. |
| Keywords: | Isoprenylcysteine methyltransferase (Icmt) Cancer target Natural products Pseudoceratina sp. Spermine alkaloid Structure elucidation |
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