344558-10-7Relevant academic research and scientific papers
Phosphonates useful as modulators of t γ(g)9γ(d)2 lymphocyte activity
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Page/Page column 12, (2010/11/24)
The invention concerns novel phosphonate derivatives, preparation method, use thereof as ligands modulating T γ9δ2 lymphocyte activity and pharmaceutical compositions comprising them.
Synthesis of vinyl pyrophosphonate analogues of farnesyl pyrophosphate: New potential inhibitors of farnesyl protein transferase
Zgani, Ibrahim,Menut, Chantal,Monte,ro, Jean Louis
, p. 654 - 661 (2007/10/03)
The synthesis of new bioisosteric analogues of farnesyl pyrophosphate where a vinyl pyrophosphonate replaced the pyrophosphate moiety is described. These compounds have been prepared using a Horner-Wadsworth-Emmons procedure and a modified Michelson react
Synthesis of farnesyl diphosphate analogues containing ether-linked photoactive benzophenones and their application in studies of protein prenyltransferases
Turek,Gaon,Distefano,Strickland
, p. 3253 - 3264 (2007/10/03)
Protein prenylation is a posttranslational lipid modification in which C15 and C20 isoprenoid units are linked to specific protein-derived cysteine residues through a thioether linkage. This process is catalyzed by a class of enzymes called prenyltransferases that are being intensively studied due to the finding that Ras protein is farnesylated coupled with the observation that mutant forms of Ras are implicated in a variety of human cancers. Inhibition of this posttranslational modification may serve as a possible cancer chemotherapy. Here, the syntheses of two new farnesyl diphosphate (FPP) analogues containing photoactive benzophenone groups are described. Each of these compounds was prepared in six steps from dimethylallyl alcohol. Substrate studies, inhibition kinetics, photoinactivation studies, and photolabeling experiments are also included; these experiments were performed with a number of protein prenyltransferases from different sources. A X-ray crystal structure of one of these analogues bound to rat farnesyltransferase illustrates that they are good substrate mimics. Of particular importance, these new analogues can be enzymatically incorporated into Ras-based peptide substrates allowing the preparation of molecules with photoactive isoprenoids that may serve as valuable probes for the study of prenylation function. Photoaffinity labeling of human protein geranylgeranyltransferase with 32P-labeled forms of these analogues suggests that the C-10 locus of bound geranylgeranyl diphosphate (GGPP) is in close proximity to residues from the β-subunit of this enzyme. These results clearly demonstrate the utility of these compounds as photoaffinity labeling analogues for the study of a variety of protein prenyltransferases and other enzymes that employ FPP or GGPP as their substrates.
