Conformational behavior of basic monomeric building units of glycosaminoglycans: isolated systems and solvent effect

Our work reports in detail the results of systematic large-scale theoretical investigations of the glycosaminoglycan building units 1-OMe DeltaIdoA-2SNa2 (1; 2H1 and 1H2 forms), 1-OMe GlcN-S6SNa2 (2), 1,4-DiOMe GlcNa (3), 1,4-DiOMe GlcN-S3S6SNa3 (4), 1,4-DiOMe IdoA-2SNa2 (5; 4C1, 1C4, and 2So conformations), and 1,4-DiOMe GlcN-S6SNa2 (6) at the BP86/TZ2P level of the density functional theory. The optimized geometries indicate that the most stable structure of these monomeric units in the neutral state is stabilized via "multifurcated" sodium bonds. The equilibrium structure of the biologically active anionic forms of the glycosaminoglycans studied changed considerably in a water solution. The computed interaction energies, DeltaE, of sodium coordinated systems 1-6 are negative and span a rather broad energy interval (from -130 to -590 kcal mol-1). Computations that include the effect of solvation indicated that in water the relative stability of Na+...ligand ionic bonds is considerably diminished. The computed interaction energy in water is small (from -20 to -53 kcal mol-1) and negative, that is, stabilizing.     

Ground Layer Adaptive Optics

We will introduce the present knowledge of the turbulence profile and in particular we will emphasise the existence of a turbulence layer close to the ground. Then we will present the concept of Ground Layer Adaptive Optics and will provide estimates of performance expected from such systems and their potential for astronomical applications. Finally we will provide practical implementation concepts for two instruments at the VLT, MUSE and HAWK-I using multi-Laser Guide Stars and a large Deformable Secondary Mirror. The latter will also be described as its use is optimum for GLAO systems. To cite this article: N. Hubin et al., C. R. Physique 6 (2005).     

Synthesis of strained cyclic peptides via an aza-Michael-acyl-transfer reaction cascade

A new method is presented to prepare strained lactams. Esterification of the C-terminus of a dipeptide with β-nitrostyrene or quinoline-type auxiliaries is followed by lactam formation by an intramolecular aza-Michael-acyl-transfer reaction cascade. Ultimately, the cyclic tetrapeptide cyclo[Phe-Tyr-Ala-Gly] has been prepared.     

Perindoprilat monohydrate

The title compound [systematic name: (1S)‐2‐((S)‐{1‐[(2S,3aS,7aS)‐2‐carboxyoctahydro‐1H‐indol‐1‐yl]‐1‐oxopropan‐2‐yl}azaniumyl)pentanoate monohydrate], C₁₇H₂₈N₂O₅·H₂O, (I)·H₂O, the active metabolite of the antihypertensive and cardiovascular drug perindopril, was obtained during polymorphism screening of perindoprilat. It crystallizes in the chiral orthorhombic space group P2₁2₁2₁, the same as the previously reported ethanol disolvate [Pascard, Guilhem, Vincent, Remond, Portevin & Laubie (1991). J. Med. Chem. 34 , 663–669] and dimethyl sulfoxide hemisolvate [Bojarska, Maniukiewicz, Sieroń, Fruziński, Kopczacki, Walczyński & Remko (2012). Acta Cryst. C 68 , o341–o343]. The asymmetric unit of (I)·H₂O contains one independent perindoprilat zwitterion and one water molecule. These interact via strong hydrogen bonds to give a cyclic R²₂(7) synthon, which provides a rigid molecular conformation. The geometric parameters of all three forms are similar. The conformations of the perhydroindole group are almost identical, but the n‐alkyl chain has conformational freedom. A three‐dimensional hydrogen‐bonding network of O—H...O and N—H...O interactions is observed in the crystal structure of (I)·H₂O, similar to the other two solvates, but because of the presence of different solvents the three crystal structures have diverse packing motifs. All three solvatomorphs are additionally stabilized by nonclassical weak C—H...O contacts.     

Enantioselective copper-catalysed propargylic substitution: synthetic scope study and application in formal total syntheses of (+)-anisomycin and (-)-cytoxazone

A copper catalyst with a chiral pyridine-2,6-bisoxazoline (pybox) ligand was used to convert a variety of propargylic esters with different side chains (R=Ar, Bn, alkyl) into their amine counterparts in very high yields and with good enantioselectivities (up to 90% enantiomeric excess (ee)). Different amine nucleophiles were applied in the reactions and the highest enantioselectivities were obtained for aniline and its analogues. Interestingly, some carbon nucleophiles could also be used and with indoles excellent ee values were obtained (up to 98% ee). The versatility of the propargylic amines obtained was demonstrated by their further elaboration to formal total syntheses of the antibiotic (+)-anisomycin and the cytokine modulator (-)-cytoxazone.     

Comparison of activated chromatography resins for protein immobilization

The adsorption of bovine serum albumin (BSA) to an immobilized camelid‐derived antibody fragment was investigated using six different activated resins, of which two are prototypes. The resins differed in base material, coupling chemistry and particle size. The adsorption, washing and desorption stage of the affinity chromatography process were taken into account. Dynamic binding capacities at 10% breakthrough ranged between 0.76 and 4.8 mg BSA/mL resin. The washing volume ranged between 2.9 and 10 column volumes. One of the resins did not concentrate BSA, while the highest concentration was 13‐fold. We present a method to rank and weigh the properties of the resins to find the optimal resin to meet specific requirements. For three of the resins the adsorption flow rate was varied, while the washing and desorption flow rate was kept the same. The dynamic binding capacity decreased with increasing flow rate, as expected. For one resin, the washing volume remained constant, but for the others it decreased with increasing adsorption flow rate. The number of column volumes required to purify a given amount of BSA increases with increasing flow rate, which indicates that higher flow rates do not necessarily speed up the process.     

Characterization of β-Galactosidase Isoforms from Bacillus circulans and Their Contribution to GOS Production

A β-galactosidase preparation from Bacillus circulans consists of four isoforms called β-gal-A, β-gal-B, β-gal-C, and β-gal-D. These isoforms differ in lactose hydrolysis and galacto-oligosaccharide (GOS) synthesis at low substrate concentrations. For this reason, using a selection of the isoforms may be relevant for GOS production, which is typically done at high substrate concentrations. At initial lactose concentrations in between 0.44 % and 0.68 % (w/w), β-gal-A showed the least oligosaccharide formation, followed by β-gal-B and β-gal-C; most oligosaccharides were formed by β-gal-D. The differences in behavior were confirmed by studying the thermodynamics of lactose conversion with isothermal titration calorimetry since especially β-gal-A showed a different profile than the other isoforms. Also during the conversion of allolactose and 4-galactosyllactose at 0.44 % and 0.61 % (w/w), respectively, β-gal-A and β-gal-D showed clear differences. In contrast to above findings, the selectivity of the isoforms did hardly differ at an initial lactose concentration of 30 % (w/w), except for a slightly higher production of galactose with β-gal-A. These differences were hypothesized to be related to the different accessibility of the active sites of the isoforms for different-sized reactants. The initial GOS formation rates of the isoforms indicate that β-gal-A and β-gal-B are the best isoforms for GOS production at high lactose concentrations.     

Gas-phase and solution conformations of selected dimeric structural units of heparin

The molecular structure of four dimeric units (D-E, E-F, F-G, and G-H) of the DEFGH structural unit of heparin, their anionic forms, and their sodium salts have been studied using the B3LYP/6-31+G(d) method. The optimized geometries indicate that the most stable structure of these dimeric units in neutral state is stabilized via "bifurcated" sodium bonds. The equilibrium structure of the biologically active anionic forms of the glycosaminoglycans studied changed considerably in a water solution. The stable-energy conformations around glysosidic bonds found for the individual dimeric species investigated are in agreement with the available experimental structural data for the structurally related heparin-derived oligosaccharides.