Comparison of three methods for fractionation and enrichment of low molecular weight proteins for SELDI-TOF-MS differential analysis

In most diseases, the clinical need for serum/plasma markers has never been so crucial, not only for diagnosis, but also for the selection of the most efficient therapies, as well as exclusion of ineffective or toxic treatment. Due to the high sample complexity, prefractionation is essential for exploring the deep proteome and finding specific markers.In this study, three different sample preparation methods (i.e., highly abundant protein precipitation, restricted access materials (RAM) combined with IMAC chromatography and peptide ligand affinity beads) were investigated in order to select the best fractionation step for further differential proteomic experiments focusing on the LMW proteome (MW inferior to 40,000 Da). Indeed, the aim was not to cover the entire plasma/serum proteome, but to enrich potentially interesting tissue leakage proteins. These three methods were evaluated on their reproducibility, on the SELDI-TOF-MS peptide/protein peaks generated after fractionation and on the information supplied.The studied methods appeared to give complementary information and presented good reproducibility (below 20%). Peptide ligand affinity beads were found to provide efficient depletion of HMW proteins and peak enrichment in protein/peptide profiles.     

Consecutive reactions with sulfoximines: a direct access to 2-sulfonimidoylylidene tetrahydrofurans and 6-sulfonimidoylmethyl-3,4-dihydro-2H-pyrans

2-Sulfonimidoylylidene tetrahydrofurans and 2-sulfonimidoylylidene-5-vinyl tetrahydrofurans were readily synthesized via a consecutive acylation/SN2 sequence with total regio- and chemoselectivity from Johnson's sulfoximine derivatives. The same consecutive reaction could also be applied to the expeditious synthesis of 6-sulfonimidoylmethyl-3,4-dihydro-2H-pyrans.     

Selective formation of dihydropyran derivatives by a tandem domino ring-closing metathesis/cross-metathesis

A ring-closing metathesis (RCM)/cross-metathesis (CM) domino reaction has been applied to esters and unsymmetrical ether prepared from 1,5-hexadien-3-ol. For the first time, dihydropyran derivatives have been obtained via a regioselective cyclization. This reaction was performed in high yield and E stereoselectivity.     

Shape transition in artificial tumors: from smooth buckles to singular creases

Using swelling hydrogels, we study the evolution of a thin circular artificial tumor whose growth is confined at the periphery. When the volume of the outer proliferative ring increases, the tumor loses its initial symmetry and bifurcates towards an oscillatory shape. Depending on the geometrical and elastic parameters, we observe either a smooth large-wavelength undulation of the swelling layer or the formation of sharp creases at the free boundary. Our experimental results as well as previous observations from other studies are in very good agreement with a nonlinear poroelastic model.     

A straightforward synthesis of (E)-δ-alkenyl-β,γ-unsaturated δ-lactones by a tandem ring-closing/cross-coupling metathesis process

The access to (E)-δ-alkenyl-β,γ-unsaturated δ-lactones starting from 3-O-(1,4-pentadienyl) 3-butenoate has been investigated by using a tandem process including two different metathesis reactions. By this way, new structures, isomers of natural compounds like argentilactone, were isolated in good yields. Reconjugation of the internal CC bond can be achieved under basic conditions to give α-pyrones.     

Budding and tubulation in highly oblate vesicles by anchored amphiphilic molecules

We studied local budding and tubulation induced in highly oblate lipid vesicles by the anchoring of either polymers having a hydrophilic backbone and grafted hydrophobic anchor groups, or by oleoyl-coenzyme A, an amphiphilic molecule important in lipid metabolism. The dynamics of bud formation, shrinkage, and readsorption is consistent with an induced spontaneous curvature coupled with local amphiphile diffusion on the membrane. We report a novel metastable state prior to bud readsorption.     

Total and formal enantioselective synthesis of lyngbic acid and hermitamides A and B

The synthesis of lyngbic acid and both hermitamides A and B, three compounds previously isolated from Lyngbya majuscula has been achieved by a cross-metathesis between 4-methoxyundec-1-ene with pent-4-enoic acid or its amides. The reaction proceeds smoothly to deliver the target molecules in appreciable yields and with a very high E selectivity as determined by NMR experiments. Allyl transfer using a camphor derived homoallylic alcohol allowed the synthesis of enantiomerically enriched starting materials.     

Shear-induced permeation and fusion of lipid vesicles

This paper introduces a novel approach to controlling membrane permeability in free unilamellar vesicles using shearing in the presence of a detergent with a large head-group to tune pore formation. Such shear-induced permeation could offer a simple means of postencapsulating bioactive molecules to prepare vesicle vectors for drug delivery. Using UV absorption, fluorescence emission, dynamic light scattering, and electron microscopy, we investigated the membrane permeability and the morphology of unilamellar lipid vesicles (diameter in the range 50-400 nm) subjected to a shear stress in the presence of a small amount of nonionic surfactant (Brij 76). Shear-induced leakage and fusion events were observed. We analyzed the significance of the vesicle size, the shear rate, and the surfactant-to-lipid ratio for the observed phenomena. The present approach is evaluated for postloading of preformed vesicles.