title: Spermatinamine, the first natural product inhibitor of isoprenylcysteine carboxyl methyltransferase, a new cancer target.
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.
authors.affiliation: Eskitis Institute, Griffith University, Brisbane, Qld 4111, Australia.
authors.forename: Malcolm S
authors.initials: MS
authors.lastname: Buchanan
authors.forename: Anthony R
authors.initials: AR
authors.lastname: Carroll
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Fechner
authors.forename: Anthony
authors.initials: A
authors.lastname: Boyle
authors.forename: Moana M
authors.initials: MM
authors.lastname: Simpson
authors.forename: Rama
authors.initials: R
authors.lastname: Addepalli
authors.forename: Vicky M
authors.initials: VM
authors.lastname: Avery
authors.forename: John N A
authors.initials: JN
authors.lastname: Hooper
authors.forename: Nancy
authors.initials: N
authors.lastname: Su
authors.forename: Huawei
authors.initials: H
authors.lastname: Chen
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Quinn
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000633:toxicity*; D001688:Biological Products / Q000737:chemistry* / Q000633:toxicity*; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000633:toxicity; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D009369:Neoplasms / Q000201:enzymology* / Q000473:pathology; D011496:Protein Methyltransferases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013096:Spermine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000633:toxicity; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000633:toxicity
chemical_list: D000970:Antineoplastic Agents; D001688:Biological Products; D004791:Enzyme Inhibitors; C525803:spermatinamine; D013096:Spermine; D014443:Tyrosine; D011496:Protein Methyltransferases; C056501:protein-S-isoprenylcysteine O-methyltransferase