Spermatinamine, the first natural product inhibitor of isoprenylcysteine carboxyl methyltransferase, a new cancer target.
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.
Buchanan
Malcolm S
MS
Eskitis Institute, Griffith University, Brisbane, Qld 4111, Australia.
Carroll
Anthony R
AR
Fechner
Gregory A
GA
Boyle
Anthony
A
Simpson
Moana M
MM
Addepalli
Rama
R
Avery
Vicky M
VM
Hooper
John N A
JN
Su
Nancy
N
Chen
Huawei
H
Quinn
Ronald J
RJ
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
D000970:Antineoplastic Agents; D001688:Biological Products; D004791:Enzyme Inhibitors; C525803:spermatinamine; D013096:Spermine; D014443:Tyrosine; D011496:Protein Methyltransferases; C056501:protein-S-isoprenylcysteine O-methyltransferase