Four new farnesyl hydroxybenzoic acid derivatives, kuhistanols E-H (1-4), were isolated from the roots of the Uzbekistan medicinal plant Ferula kuhistanica. The structures of the new compounds were elucidated based on spectroscopic and chemical evidence.

Farnesyl diphosphate synthase (FPPS) catalyses the formation of farnesyl diphosphate from dimethylallyl diphosphate and isopentenyl diphosphate and is an RNAi-validated drug target in Trypanosoma brucei, the causative agent of African sleeping sickness. A T. brucei FPPS (390 amino acids) has been expressed in Escherichia coli and the recombinant protein has been crystallized in the absence and ...

Matrix metalloproteinase-1 (MMP-1) activity has been linked to numerous disease processes from arthritis to ulcer. Its proteolytic activity has been implicated inconsistently in different steps of tumourigenesis and metastasis. The discrepancies may be attributable to our limited understanding of MMP-1 production, cellular trafficking, secretion and local activation. Specifically, regulation of...

BACKGROUND The use of integrating viral vectors in Gene therapy clinical trials has pointed out the problem of the deleterous effect of the integration of the ectopic gene to the cellular genome and the safety of this strategy. We proposed here a way to induce the death of gene modified cells upon request by acting on a pro-apoptotic protein cellular localization and on the activation of its ap...

Sesquiterpene skeletal complexity in nature originates from the enzyme-catalyzed ionization of (trans,trans)-farnesyl diphosphate (FPP) (1a) and subsequent cyclization along either 2,3-transoid or 2,3-cisoid farnesyl cation pathways. Tobacco 5-epi-aristolochene synthase (TEAS), a transoid synthase, produces cisoid products as a component of its minor product spectrum. To investigate the cryptic...

The multiproduct sesquiterpene synthase MtTPS5 from Medicago truncatula catalyzes the conversion of farnesyl diphosphate (FDP) into a complex mixture of 27 terpenoids. 3-Bromo substrate analogues of geranyl diphosphate (3-BrGDP) and farnesyl diphosphate (3-BrFDP) were evaluated as substrates of MTPS5 enzyme. Kinetic studies demonstrated that these compounds were highly potent competitive inhibi...

Analogues of farnesyl diphosphate (FPP, ) containing phenyl substituents in place of methyl groups have been prepared in syntheses that feature use of a Suzuki-Miyaura reaction as a key step. These analogues were found not to act as substrates of the sesquiterpene cyclase aristolochene synthase from Penicillium roqueforti (AS). However, they were potent competitive inhibitors of AS with K(I)-va...