183376-22-9Relevant academic research and scientific papers
Synthesis and Biological Activity of Photoactivatable N-Ras Peptides and Proteins
Voelkert, Martin,Uwai, Koji,Tebbe, Andreas,Popkirova, Boriana,Wagner, Melanie,Kuhlmann, Juergen,Waldman, Herbert
, p. 12749 - 12758 (2007/10/03)
A modular strategy for the assembly of farnesylated N-Ras heptapeptides carrying a photoactivatable benzophenone (BP) group within the lipid residue is described. This strategy is based on the fragment condensation of a N-terminal hexapeptide synthesized
Photoactive analogs of farnesyl pyrophosphate containing benzoylbenzoate esters: Synthesis and application to photoaffinity labeling of yeast protein farnesyltransferase
Gaon, Igor,Turek, Tammy C.,Weller, Valerie A.,Edelstein, Rebecca L.,Singh, Satinder K.,Distefano, Mark D.
, p. 7738 - 7745 (2007/10/03)
Farnesyl pyrophosphate (FPP) is involved in a large number of cellular processes including the prenylation of transforming mutants of Ras proteins implicated in cancer. Photoactive analogs could provide useful information about enzyme active sites that bind farnesyl pyrophosphate; however, the availability of such compounds is extremely limited. Molecules that incorporate benzophenone moieties are attractive photoaffinity labeling reagents because of their useful photochemical properties. Here, the syntheses of two compounds, 3a and 3b, containing para- and meta-substituted benzoylbenzoates are described. Compounds 3a and 3b are competitive inhibitors (with respect to FPP) of yeast protein farnesyltransferase (PFTase) with K(i) values of 910 and 380 nM, respectively. Both compounds inactivate PFTase upon photolysis, resulting in as much as 44% inactivation of enzyme activity. Photolysis of PFTase in the presence of [32P]3a or of [32P]3b results in preferential labeling of the β subunit, suggesting that this subunit is involved in prenyl group recognition. These compounds should be valuable tools for studying enzymes that utilize FPP as a substrate.
