S6 Kinase- and β-TrCP2-Dependent Degradation of p19Arf Is Required for Cell Proliferation.

The kinase mTOR (mammalian target of rapamycin) promotes translation as well as cell survival and proliferation under nutrient-rich conditions. Whereas mTOR activates translation through ribosomal protein S6 kinase (S6K) and eukaryotic translation initiation factor 4E-binding protein (4E-BP), how it facilitates cell proliferation has remained unclear. We have now identified p19(Arf), an inhibitor of cell cycle progression, as a novel substrate of S6K that is targeted to promote cell proliferation.

Enantioselective total syntheses of pygmaeocins B and C.

The first enantioselective total syntheses of pygmaeocins B and C have been accomplished using an efficient and highly diastereoselective intramolecular Heck cyclization for the construction of a quaternary stereogenic center and the functionalized A-ring of the natural products as the key step.

Diastereoselective intramolecular carbamoylketene/alkene [2 + 2] cycloaddition: enantioselective access to pyrrolidinoindoline alkaloids.

A novel and highly diastereoselective intramolecular carbamoylketene/alkene [2 + 2] cycloaddition has been developed, and the methodology was successfully applied to the enantioselective syntheses of (-)-esermethole and Takayama's intermediate for (+)-psychotrimine.

Improved performance by replacing iminodiacetic residues with glyceryl residues in symmetrically branched oligoglycerols.

Synthesis of a symmetrically branched diglycerol (BGL002, involving one iminodiacetic residue) as a G2 dendron, and the tetradecaglycerol (BGL014, involving one iminodiacetic residue) as a G4 dendron, is described. Several members of the BGL family of G2-G4 dendrons were assembled, with G2 bearing four hydroxyl groups at the terminus region, G3 bearing eight, and G4 bearing sixteen. It is noteworthy that triglycerol (BGL003, including no iminodiacetic residue), has a water-solubility ten times higher than BGL002, and the liposome surrounded by BGL014 has a duration period in blood vessel roughly two times longer than the liposome surrounded by dodecaglycerol (BGL012, including three iminodiacetic residues).

Modification of protein with BGL06, a novel branched oligoglycerol derivative.

A branched oligoglycerol derivative, BGL06, with a cascade-like structure of glycerol units was used as a novel reagent for protein modification. Modification reaction with a recombinant human granulocyte-colony stimulating factor derivative, ND28, was carried out successfully in aqueous conditions to obtain a coupled form, BGL06-ND28. Characterization of the modified ND28 suggests that two types of products were obtained by controlling the reaction; one was H(BGL06)-ND28, a highly modified version coupled with 4.

Design and synthesis of highly potent and selective human peroxisome proliferator-activated receptor alpha agonists.

A combination of benzoxazole, phenoxyalkyl side chain, and phenoxybutyric acids was identified as a highly potent and selective human peroxisome proliferator-activated receptor alpha (PPARalpha) agonist. The synthesis, structure-activity relationship (SAR) studies, and in vivo activities of the representative compounds are described.