Two Distinct Structures of Membrane-Associated Homodimers of GTP- and GDP-Bound KRAS4B Revealed by Paramagnetic Relaxation Enhancement

KRAS homo-dimerization has been implicated in the activation of RAF kinases, however, the mechanism and structural basis remain elusive. We developed a system to study KRAS dimerization on nanodiscs using paramagnetic relaxation enhancement (PRE) NMR spectroscopy, and determined distinct structures of membrane-anchored KRAS dimers in the active GTP- and inactive GDP-loaded states. Both dimerize through an α4–α5 interface, but the relative orientation of the protomers and their contacts differ substantially. Dimerization of KRAS-GTP, stabilized by electrostatic interactions between R135 and E168, favors an orientation on the membrane that promotes accessibility of the effector-binding site. Remarkably, “cross”-dimerization between GTP- and GDP-bound KRAS molecules is unfavorable. These models provide a platform to elucidate the structural basis of RAF activation by RAS and to develop inhibitors that can disrupt the KRAS dimerization. The methodology is applicable to many other farnesylated small GTPases.     

Mass migration on a polymer surface caused by photoinduced molecular rotation

We demonstrated the formation of a photoinduced surface relief grating using thin films comprising a photochromic molecular motor, 9-(2-phenyl-2,3-dihydro-cyclopenta[a]naphthalen-1-ylidene)-9H-fluorene. Results show that mass migration occurred by patterned light irradiation prepared from interfered laser beams and a photomask.     

Halichonadins K and L, new dimeric sesquiterpenoids from a sponge Halichondria sp

Two new structurally unique dimeric sesquiterpenoids, halichonadins K (1) and L (2), were isolated from an Okinawan marine sponge Halichondria sp. The structures of 1 and 2 were elucidated on the basis of spectroscopic analysis including a single crystal X-ray diffraction analysis and chemical conversion. Halichonadins K (1) and L (2) are homodimers of the eudesmane sesquiterpene linked with a piperidine ring through amide bonds. Halichonadin K (1) showed moderate cytotoxicity against KB cells.     

Powder-to-powder polycondensation of natural saccharides. Facile preparation of highly branched polysaccharides

Solid-state polycondensation of a natural saccharide was found to take place in the presence of H3PO4(5 mol%) at 110 degrees C under a N2 flow, giving a highly branched polysaccharide (conv. 11-84%, Mw = 1400-19000, Mn = 1200-3700); the reaction mixture was powdery throughout the polymerization. Interestingly, alpha- and beta-anomers showed different polymerization behaviour; the former was polymerized more slowly, however, they gave comparable molecular weight polymers. The polysaccharide product was per-O-methylated and subjected to structure analyses. The acid-hydrolysis products, the partially O-methylated monosaccharides, suggested that the polysaccharide products have highly branched structures. MALDI-TOF mass analysis revealed that intramolecular glycosylation and acetal exchange reactions are involved in the polymerization mechanism.     

Preparation of Weinreb amides using 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (DMT-MM)

Weinreb amides were successfully prepared from the corresponding carboxylic acids using 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (DMT-MM) in the solvents, methanol, isopropyl alcohol, and acetonitrile, which can solubilize DMT-MM. A variety of carboxylic acids were converted to the corresponding Weinreb amides in excellent yields by simply mixing with DMT-MM and N,O-dimethylhydroxylamine hydrochloride.     

High-speed living polymerization with a new catalyst system based on metalloporphyrin

A novel catalyst system composed of aluminium porphyrin and an organoaluminium compound with bulky substituents brings about high-speed living polymerizations of epoxide, lactone, and methacrylic ester to give the polymers with controlled molecular weight.     

‘Immortal’ polymerization of epoxide with metalloporphyrin catalyst

Aluminum porphyrin is an excellent initiator for the polymerization of epoxides to give polyethers with narrow molecular weight distribution, even in the presence of protic compounds such as alcohols, carboxylic acids, and hydrogen chloride. The number of polymer molecules is higher than that of initiator molecules. By taking advantage of the “immortal” nature of this polymerization, a novel, efficient procedure for the synthesis of block copolymers and end-reactive polymers with narrow molecular weight distribution is developed.