- Synthesis and biological evaluation of cycloalkylidene carboxylic acids as novel effectors of Ras/Raf interaction
-
The protooncogenes Ras and Raf play important roles in signal transduction pathways regulated by mitogen-activated protein kinases. Mutations of Ras that arrest the protein in its active state are frequently implicated in tumor formation. We used Ras and Raf proteins in the yeast two-hybrid system to search for natural or synthesized substances capable of modulating Ras/Raf interaction by specifically binding to one of the interacting partners. We found that cycloalkylidene carboxylic acids enhanced Ras/Raf interaction by acting on the cysteine-rich domain of Raf. Several analogues of the active substance 2-cyclohexylidene propanoic acid were synthesized and the importance of the semicyclic double bond in the stabilization of Ras/Raf interaction was demonstrated. Variation of the size and the substituents of the cyclic system as well as the length of the carboxylic acid resulted in enhanced Ras/Raf interaction.
- Friese, Anke,Hell-Momeni, Katja,Zündorf, Ilse,Winckler, Thomas,Dingermann, Theodor,Dannhardt, Gerd
-
p. 1535 - 1542
(2007/10/03)
-
- A New Entry to the C12H12 Energy Surface: Pyrolysis and Photolysis of trans-β-nona-2,4,6-trienyl>acrolein Tosylhydrazone Saltz
-
Thermal decomposition of the lithium salt of trans-β-nona-2,4,6-trienyl>acrolein tosylhydrazone (8) results in the formation of pentacyclo2,12.03,7.04,11>dodeca-5,9-diene (12), exo- and endo-tricyclo2,5>dodeca-3,7,9,11-tetraenes (9 and 10), 1,2-benzocycloocta-1,3,7-triene (11), and syn- and anti-9-(5-pyrazolyl)bicyclonona-2,4,7-trienes (14 and 13).The low-temperature photolysis of the sodium salt of tosylhydrazone 8 gives anti-9-(2-cyclopropen-1-yl)bicyclonona-2,4,6-triene (20), which affords pentacyclo2,4.03,10.05,9>dodeca-6-11-diene (22) on thermolysis.Hydrocarbon 12 was formed in the photolysis of the sodium salt of trans-β-nona-2,4,7-trienyl>acrolein tosylhydrazone (15; available by thermal rearrangement of tosylhydrazone 8) as the sole C12H12 product.Structure determinations and mechanistic investigations are discussed.
- Farnum, D. G.,Ghandi, M.,Raghu, S.,Reitz, T.
-
p. 2598 - 2607
(2007/10/02)
-