367522-58-5Relevant academic research and scientific papers
Synthesis of α-hydroxy ketones from terpene aldehydes
Schueler, Martin,Zorn, Holger,Slawin, Alexandra M. Z.,Berger, Ralf G.
, p. 2591 - 2600 (2004)
Unsymmetrically substituted α-hydroxy ketones possessing isoprenoid units within the molecule were synthesised from commercially available terpene aldehydes. The synthesis was applicable to α,β-unsaturated aldehydes and afforded the respective α-hydroxy-m
Inactivation of protein farnesyltransferase by active-site-targeted dicarbonyl compounds
Okolotowicz, Karl J.,Lee, Wei-Jen,Hartman, Rosemarie F.,Kim, Ann Y.,Ottersberg, Steven R.,Robinson Jr., Dale E.,Lefler, Scott R.,Rose, Seth D.
, p. 194 - 202 (2007/10/03)
Upon farnesylation by protein farnesyltransferase (FTase), key proteins become compartmentalized in cells. For example, cell membrane localization is essential for the mitogenic role of mutant Ras protein, which acts as a switch for cancer cell proliferation. We report that α-dicarbonyl compounds derived from the isoprenoid skeleton or other hydrophobic groups potently obstruct farnesylation of a Ras model peptide by human recombinant FTase in vitro. A geranyl-derived isoprenoid diketone, 5,9-dimethyl-8-decene-2,3-dione, at 17 μM caused a 62% reduction in FTase activity after 30 minutes. A farnesyl-derived isoprenoid diketone, 5,9,13-trimethyl-8,12-tetradecadiene-2,3-dione, at 93 μM caused a 94% reduction after 30 minutes. Other dicarbonyl compounds found to be effective against FTase in vitro were (±)-6-(camphorquinone-10-sulfonamido)-hexanoic acid, 4,4′-biphenyldiglyoxaldehyde, dehydroascorbic acid 6-palmitate, 2-oxododecanal, and phenylglyoxal. Higher concentrations of the α-dicarbonyl compound resulted in more rapid and more extensive inactivation. These findings demonstrate that α-dicarbonyl compounds targeted to FTase interfere with protein farnesylation in vitro and may lead to derivatives that have utility as chemotherapeutic agents.
