Synthesis of enantiopure 4-hydroxypipecolate and 4-hydroxylysine derivatives from a common 4,6-dioxopiperidinecarboxylate precursor

tert-Butyl 2-substituted 4,6-dioxo-1-piperidinecarboxylates 4 have been prepared in good yield starting from Boc-Asp-O(t)Bu and other beta-amino acids. By analogy with chiral tetramic acids, their reduction by NaBH(4) in CH(2)Cl(2)/AcOH afforded the corresponding cis-4-hydroxy delta-lactams in good yield and stereoselectivity (68-98% de). In the absence of the A(1,3) strain (reduction of 6-substituted 2,4-dioxo-1-piperidines 7), the cis-4-hydroxy isomer was still obtained as the major product but the de values were consistently lower. 4-Hydroxy-6-oxo-1,2-piperidinedicarboxylate 2a, readily accessible from Boc-Asp-O(t)Bu (three steps, 63% overall yield), has proven to be an excellent building block for the synthesis of cis- and trans-4-hydroxypipecolates 17 and 24 (52 and 36% overall yield, respectively) and for the synthesis of a protected 4-hydroxylysine derivative 29 (41% overall yield).     

Protein polymer conjugates: improving the stability of hemoglobin with poly(acrylic acid)

The synthesis, characterization, and evaluation of a novel polymer-protein conjugate are reported here. The covalent conjugation of high-molecular weight poly(acrylic acid) (PAA) to the lysine amino groups of met-hemoglobin (Hb) resulted in the covalent conjugation of Hb to PAA (Hb-PAA conjugate), as confirmed by dialysis and electrophoresis studies. The retention of native-like structure of Hb in Hb-PAA was established from Soret absorption, circular dichroism studies, and the redox activity of the iron center in Hb-PAA. The peroxidase-like activities of the Hb-PAA conjugate further confirmed the retention of Hb structure and biological activity. Thermal denaturation of the conjugate was investigated by differential scanning calorimetry and steam sterilization studies. The Hb-PAA conjugate indicated an improved denaturation temperature (T(d)) when compared to that of the unmodified Hb. One astonishing observation was that polymer conjugation significantly enhanced the Hb-PAA storage stability at room temperature. After 120 h of storage at room temperature in phosphate-buffered saline (PBS) at pH 7.4, for example, Hb-PAA retained 90% of its initial activity and unmodified Hb retained <60% of its original activity under identical conditions of buffer, pH, and temperature. Our conjugate demonstrates the key role of polymers in enhancing Hb stability via a very simple, efficient, general route. Water-swollen, lightly cross-linked, stable Hb-polymer nanogels of 100-200 nm were produced quickly and economically by this approach for a wide variety of applications.     

BSDEs with stochastic Lipschitz condition and quadratic PDEs in Hilbert spaces

This paper is devoted to real valued backward stochastic differential equations (BSDEs for short) with generators which satisfy a stochastic Lipschitz condition involving BMO martingales. This framework arises naturally when looking at the BSDE satisfied by the gradient of the solution to a BSDE with quadratic growth in Z$Z$. We first prove an existence and uniqueness result from which we deduce the differentiability with respect to parameters of solutions to quadratic BSDEs. Finally, we apply these results to prove the existence and uniqueness of a mild solution to a parabolic partial differential equation in Hilbert space with nonlinearity having quadratic growth in the gradient of the solution.     

Mimicking helical antibacterial peptides with nonpeptidic folding oligomers

Unnatural oligomeric scaffolds designed to adopt defined secondary structures (e.g., helices), while retaining the chemical diversity of amino acid side chains, are of practical value to elaborate functional mimetics of bioactive alpha-polypeptides. Enantiopure N,N'-linked oligoureas as short as seven residues long have been previously shown to fold into a stable helical structure, stabilized by 12- and 14-membered H-bonded rings. We now report that eight-residue oligoureas designed to mimic globally amphiphilic alpha-helical host-defense peptides are effective against both gram-negative and gram-positive bacteria (including methicillin-resistant Staphylococcus aureus [MRSA]) and exhibit selectivity for bacterial versus mammalian cells. Circular dichroism (CD) spectroscopy studies suggest enhanced helical propensity of oligoureas in the presence of phospholipid vesicles. The utility of this new class of nonpeptidic foldamers for biological applications is highlighted by high resistance to proteolytic degradation.     

Quadratic BSDEs with convex generators and unbounded terminal conditions

In Briand and Hu (Probab Theory Relat Fields 136(4):604–618, 2006), the authors proved an existence result for BSDEs with quadratic generators with respect to the variable z and with unbounded terminal conditions. However, no uniqueness result was stated in that work. The main goal of this paper is to fill this gap. In order to obtain a comparison theorem for this kind of BSDEs, we assume that the generator is convex with respect to the variable z. Under this assumption of convexity, we are also able to prove a stability result in the spirit of the a priori estimates stated in Karoui et al. (Math Finance 7(1):1–71, 1997). With these tools in hands, we can derive the nonlinear Feynman–Kac formula in this context.     

Activation of a Sweet Taste Receptor by Oleanane-Type Glycosides from Wisteria sinensis

The phytochemical study of Wisteria sinensis (Sims) DC. (Fabaceae), commonly known as the Chinese Wisteria, led to the isolation of seven oleanane-type glycosides from an aqueous-ethanolic extract of the roots. Among the seven isolated saponins, two have never been reported before: 3-O-α-L-rhamnopyranosyl-(1→2)-β-D-glucopyranosyl-(1→2)-β-D-glucuronopyranosyl-22-O-acetylolean-12-ene-3β,16β,22β,30-tetrol, and 3-O-β-D-xylopyranosyl-(1→2)-β-D-glucuronopyranosylwistariasapogenol A. Based on the close structures between the saponins from W. sinensis, and the glycyrrhizin from licorice, the stimulation of the sweet taste receptor TAS1R2/TAS1R3 by these glycosides was evaluated.     

A micro gas preconcentrator with improved performance for pollution monitoring and explosives detection

This paper presents the optimization of a micro gas preconcentrator based on a micro-channel in porous and non-porous silicon filled with an adequate adsorbent. This micro gas preconcentrator is both applicable in the fields of atmospheric pollution monitoring (Volatil organic compounds—VOCs) and explosives detection (nitroaromatic compounds). Different designs of micro-devices and adsorbent materials have been investigated since these two parameters are of importance in the performances of the micro-device. The optimization of the device and its operation were driven by its future application in outdoor environments. Parameters such as the preconcentration factor, cycle time and the influence of the humidity were considered along the optimization process. As a result of this study, a preconcentrator with a total cycle time of 10 min and the use of single wall carbon nanotubes (SWCNTs) as adsorbent exhibits a good preconcentration factor for VOCs with a limited influence of the humidity. The benefits of using porous silicon to modify the gas desorption kinetics are also investigated.     

Experimental study of relativistic correlations and QED effects in heliumlike Krypton ions

The energies of the 2^3,1P₁–1¹S₀ transitions in heliumlike Krypton have been measured at GANIL, using a 35 MeV/A krypton beam and a flat crystal Bragg spectrometer. Direct comparison with hydrogenlike Lyman α₁ emitted by the same beam enables to reach an accuracy of 20ppm. This measurement is then sensitive to quantum-electrodynamic (QED) and magnetic correlation effects.