Synthesis of a (+)-anatoxin-a analogue for monoclonal antibodies production

Anatoxin-a analogue was prepared by resolution of aminoacid 1 using chiral (R)-4-phenyl-oxazolidin-2-thione as derivatizing agent. X-ray diffraction of a diastereomer allowed us to determine its absolute configuration. The synthesis could then be completed in few steps followed by introduction of an amide linker bearing a terminal alkyne in order to attach a carrier protein for monoclonal antibodies production.     

Black foam films from aqueous solutions of a mixture of phospholipids and a permeation enhancer

The influence of a permeation enhancer on the properties of phospholipid black foam films has been studied through the combination of three complementary techniques: surface tension measurements, X-ray reflectivity, and the "diminishing bubble" method. This permeation enhancer is said to optimize the delivery of active ingredients into or through the stratum corneum: the 4-decyl oxazolidin-2-one. We made films of a complex phospholipid mixture that mimic the behavior of the enhancer in a membrane cell. Mixed phospholipids/4-decyl oxazolidin-2-one/NaCl solutions were studied with various 4-decyl oxazolidin-2-one concentrations. Stable black films were obtained and their thicknesses examined. The evolution of the coefficient of gas permeability with 4-decyl oxazolidin-2-one concentration is also addressed.     

Maturation of the [FeFe]-Hydrogenase: Direct Transfer of the (κ3-cysteinate)FeII(CN)(CO)2 Complex B from HydG to HydE

[FeFe]-hydrogenases efficiently catalyze the reversible oxidation of molecular hydrogen. Their prowess stems from the intricate H-cluster, combining a [Fe₄S₄] center with a binuclear iron center ([2Fe]_H). In the latter, each iron atom is coordinated by a CO and CN ligand, connected by a CO and an azadithiolate ligand. The synthesis of this active site involves a unique multiprotein assembly, featuring radical SAM proteins HydG and HydE. HydG initiates the transformation of L-tyrosine into cyanide and carbon monoxide to generate complex B, which is subsequently transferred to HydE to continue the biosynthesis of the [2Fe]_H-subcluster. Due to its instability, complex B isolation for structural or spectroscopic characterization has been elusive thus far. Nevertheless, the use of a biomimetic analogue of complex B allowed circumvention of the need for the HydG protein during in vitro functional investigations, implying a similar structure for complex B. Herein, we used the HydE protein as a nanocage to encapsulate and stabilize the complex B product generated by HydG. Using X-ray crystallography, we successfully determined its structure at 1.3 Å resolution. Furthermore, we demonstrated that complex B is directly transferred from HydG to HydE, thus not being released into the solution post-synthesis, highlighting a transient interaction between the two proteins.     

Solid-phase synthesis of alpha-Gal epitopes: on-resin analysis of solid-phase oligosaccharide synthesis with 19F NMR spectroscopy

A route for solid-phase synthesis of the alpha-Gal epitopes Gal(alpha1-3)Gal(beta1-4)Glc and Gal(alpha1-3)Gal(beta1-4)GlcNAc is described. These trisaccharide antigens are responsible for hyperacute rejection in xenotransplantation of porcine organs. Optimization of the solid-phase synthesis relied on use of fluorinated protective groups for the carbohydrate building blocks and use of a fluorinated linker. This allowed convenient on-resin analysis of the reactions with gel-phase (19)F NMR spectroscopy. Conditions were established which allowed reductive ring-opening of 4,6-O-benzylidene acetals to be performed on the solid phase with high regioselectivity to furnish the corresponding 6-O-benzyl ethers. It was found that glycosylations could be conveniently carried out by using thioglycosides as donors with N-iodosuccinimide and trifluoromethanesulfonic acid as the promoter system. With use of these conditions a challenging alpha-glycosidic linkage was successfully installed with complete stereoselectivity in the final glycosylation. It was also established that fluorinated benzoates, benzyl ethers, and benzylidene acetals display almost identical chemical properties as their nonfluorinated counterparts, a finding that is essential for future use of fluorinated protective groups in solid-phase oligosaccharide synthesis.     

Rotational intermittency and turbulence induced lift experienced by large particles in a turbulent flow

The motion of a large, neutrally buoyant, particle freely advected by a turbulent flow is determined experimentally. We demonstrate that both the translational and angular accelerations exhibit very wide probability distributions, a manifestation of intermittency. The orientation of the angular velocity with respect to the trajectory, as well as the translational acceleration conditioned on the spinning velocity, provides evidence of a lift force acting on the particle.     

Experimental demonstration of noninvasive transskull adaptive focusing based on prior computed tomography scans

Developing minimally invasive brain surgery by high-intensity focused ultrasound beams is of great interest in cancer therapy. However, the skull induces strong aberrations both in phase and amplitude, resulting in a severe degradation of the beam shape. Thus, an efficient brain tumor therapy would require an adaptive focusing, taking into account the effects of the skull. In this paper, we will show that the acoustic properties of the skull can be deduced from high resolution CT scans and used to achieve a noninvasive adaptive focusing. Simulations have been performed with a full 3-D finite differences code, taking into account all the heterogeneities inside the skull. The set of signals to be emitted in order to focus through the skull can thus be computed. The complete adaptive focusing procedure based on prior CT scans has been experimentally validated. This could have promising applications in brain tumor hyperthermia but also in transcranial ultrasonic imaging.