Nano-Fibrous Networks from Co-Assembly of Amphiphilic Peptide and Polyelectrolyte.

Organize the matter on an increasingly small scale is sought in order to increase the performance of materials. In the case of porous materials, such as filtration membranes, a compromise must be found between the selectivity provided by this nanostructuring and a permeability in particular linked to the existing pore volume. In this work, we propose an innovative waterborne approach consisting in co-assembling peptide amphiphiles (PA) which will provide nanostructuring and polyelectrolytes which will provide them with sufficient mechanical properties to sustain water pressure. C16-V3A3K3G-NH2 PA nanocylinders were synthesized and co-assembled with poly(sodium 4-styrenesulfonate) (PSSNa) into porous nano-fibrous network via electrostatic interactions. The ratio between C16-V3A3K3G-NH2 and PSSNa was studied to optimize the material structure. Since spontaneous gelation between the two precursors does not allow the material to be shaped, various production methods have been studied, in particular via tape casting and spray-coating. Whereas self-supported membranes were mechanically weak, co-assemblies supported onto commercial ultrafiltration membranes could sustain water pressure up to 3 bars while a moderate permeability was measured confirming the existence of a percolated network. The produced membrane material falls into the ultrafiltration range with a pore radius of about 7.6 nm.

Characterization of l-Theanine Excitatory Actions on Hippocampal Neurons: Toward the Generation of Novel N-Methyl-d-aspartate Receptor Modulators Based on Its Backbone.

l-Theanine (or l-γ-N-ethyl-glutamine) is the major amino acid found in Camellia sinensis. It has received much attention because of its pleiotropic physiological and pharmacological activities leading to health benefits in humans, especially. We describe here a new, easy, efficient, and environmentally friendly chemical synthesis of l-theanine and l-γ-N-propyl-Gln and their corresponding d-isomers. l-Theanine, and its derivatives obtained so far, exhibited partial coagonistic action at N-methyl-d-aspartate (NMDA) receptors, with no detectable agonist effect at other glutamate receptors, on cultured hippocampal neurons. This activity was retained on NMDA receptors expressed in Xenopus oocytes. In addition, both GluN2A and GluN2B containing NMDA receptors were equally modulated by l-theanine. The stereochemical change from l-theanine to d-theanine along with the substitution of the ethyl for a propyl moiety in the γ-N position of l- and d-theanine significantly enhanced the biological efficacy, as measured on cultured hippocampal neurons. l-Theanine structure thus represents an interesting backbone to develop novel NMDA receptor modulators.

α-Halogenated oxaphosphinanes: Synthesis, unexpected reactions and evaluation as inhibitors of cancer cell proliferation.

This paper describes the preparation and the biological evaluation of α-halogenated oxaphosphinanes. These halogen derivatives were synthetized from a short and stereoselective synthetic sequence starting by previously described hydroxy-precursors 1 and 2 with respectively a glucose and mannose-like configuration. The in vitro biological tests of these unnatural halogenated phosphinosugars, on several cell lines, highlighted, for some of them, their antiproliferative and anti migration and invasion properties at nanomolar concentration.

C-glycoside mimetics inhibit glioma stem cell proliferation, migration, and invasion.

This paper reports the design and synthesis of C-glycoside mimetics (d-glycero-d-talo- and d-glycero-d-galactopyranose analogues), a subset of the recently published phostines, belonging to the [1,2]oxaphosphinane core. Eighteen new compounds were tested against 11 cancer cell types belonging to six categories of tumor tissues and three different species. The hit compound 5.3d inhibited invasion and migration of both GBM stem cells (Gli7 and Gli4) and GBM cancer cell lines (C6, SNB75) on fibronectin, vitronectin, and laminin. Ki values for Gli7 and Gli4 migration inhibition on fibronectin were 16 and 31 nM respectively. Ki values for invasion inhibition in a 3D system were 46 nM for Gli7 and 290 nM for Gli4. These activities were associated with an antiproliferative effect on Gli4 (EC50 = 5.20 µM) and Gli7 (EC50 = 2.33 µM). In conclusion, the heptopyranose mimetic 5.3d, devoid of toxicity on astrocyte and cortical neuron cultures at concentrations below 100 µM, opens new therapeutic perspectives against glioblastoma.

Electrochemical grafting of long spacer arms of hexamethyldiamine on a screen printed carbon electrode surface: application in target induced ochratoxin A electrochemical aptasensor.

A novel strategy based on direct electrochemistry of amino group on screen printed carbon electrode surface (SPCE) was purposed. The purposed method was employed for the label free detection of ochratoxin A (OTA). A long spacer arm of hexamethyldiamine was immobilized on SPCE via electrochemical oxidation of its terminal amino-group. The activated carboxy-aptamer was covalently linked to other amino terminal group of immobilized hexamethyldiamine. The designed immobilized macromolecules resulted in the formation of long clusters on SPCE surface, while aptamer acted as gate to block the entrance of these clusters. The aptamer gates were closed due to change in conformation of aptamer upon target analyte binding, decreasing the electrochemical signal. The decrease in electrochemical signal was used for the detection of target molecule.

Concomitant polymorphism in the stereoselective synthesis of a ß-benzyl-ß-hydroxyaspartate analogue.

Two concomitant polymorphs, (I) and (II), of a ß-benzyl-ß-hydroxyaspartate analogue [systematic name: dibenzyl 2-benzyl-2-hydroxy-3-(4-methylphenylsulfonamido)succinate], C(32)H(31)NO(7)S, crystallize from a mixture of ethyl acetate and cyclohexane at ambient temperature. The structure of (I) has triclinic (P-1) symmetry and that of (II) monoclinic (P2(1)/c) symmetry. Both crystal structures are made up of a stacking of homochiral racemic dimers (2S,3S and 2R,3R) which are internally connected by a similar R(2)(2)(9) hydrogen-bonding pattern consisting of intermolecular N-H...O and O-H...O hydrogen bonds. The centroid of the racemic dimer lies on an inversion centre. The main structural difference between the two polymorphs is the conformational orientation of two of the four aromatic rings present in the molecule. Polymorph (II) is found to be twinned by reticular merohedry with twin index 3 and twin fractions 0.854 (1) and 0.146 (1).

threo-Diethyl 2-ethyl-2-hy-droxy-3-(4-methyl-benzene-sulfonamido)-succinate.

The asymmetric unit of the title compound, C(17)H(25)NO(7)S, contains two independent mol-ecules, which are enanti-omers forming a hydrogen-bonded dimer associated with two R(2) (2)(7) patterns. In each mol-ecule, one ethyl group from the two available ethyl ester functional groups is disordered. In one mol-ecule, the ethyl group of the ester function from an α-carb-oxy-lic acid is positionally disordered over two sets of sites with occupancies of 0.66:0.34. In the second mol-ecule, it is the ethyl group in the γ-ester function that is disordered over two sets of sites with occupancies of 0.58:0.42.

Homoleptic gallium(III) and indium(III) aminoalkoxides as precursors for sol-gel routes to metal oxide nanomaterials.

New homoleptic aminoalkoxides of gallium(III) and indium(III) of the types M4{(OC2H4)2NMe}6 [M = Ga (1), In (2)] and [Ga{(OC2H4)3N}]n (3), as well as a previously described Ga2(OC2H4NMe2)6 (A) have been prepared by isopropoxo(chloro)-aminoalkoxo exchange reactions and characterised by elemental analyses, FT-IR and 1H NMR spectroscopy. Formation of a star-shaped Ga[Ga{mu-eta3:eta1-(OC2H4)2NMe}2]3 (1.4CHCl3) and a zigzag linear In4{mu-eta3:eta1-(OC2H4)2NMe}6 (2.6CHCl3), as revealed by X-ray single crystal structures, reflects the structural diversity among N-methyldiethanolaminate derivatives. Their hydrolyses in boiling water, either in presence or absence of tetraalkylamonium bromide, have been studied and, for gallium derivatives, compared with similar hydrolytic reactions of Ga(OiPr)3. The hydrolysed products were studied by FT-IR, TG-DTA and XRD techniques. For gallium derivatives, transition from orthorhombic Ga(O)OH phase of as-prepared powder to phase pure rhombohedral- and monoclinic-Ga2O3 occurred at about 500 degrees C and 700 degrees C, respectively, whereas cubic In(OH)3 phase of as-prepared powder of 2 was converted to cubic In2O3 at 250 degrees C. Partial hydrolyses were also performed and evolution of the particle size in solution was recorded by light scattering measurements. Various sol-gel processing parameters such as concentration and hydrolysis ratio (h) were studied in order to stabilise nano-sized colloidal suspensions for access to thin films by spin coating. The N-methyldiethanolamine derivatives 1 and 2 were found to be the most suitable candidates for sol-gel processing. The transparent Ga2O3 and In2O3 films obtained on glass or Si wafers from spin-coating of 1 and 2, respectively, were characterised by SEM, EDX and XRD.

Total structure and inhibition of tumor cell proliferation of laxaphycins.

From a mixed assemblage of Lyngbya majuscula rich marine cyanobacteria, we isolated a series of cell growth inhibitory cyclic peptides. The structures of the two major components, laxaphycins A (1) and B (2), and of two minor peptides, laxaphycins B2 (3) and B3 (4), were determined by spectroscopic methods and degradative analysis. Absolute configurations of natural and nonproteinogenic amino acids were determined by a combination of hydrolysis, synthesis of noncommercial residues, chemical derivatization, and HPLC analysis. The organism producing the laxaphycins was identified as the cyanobacterium Anabaena torulosa. The antiproliferative activity of laxaphycins was investigated on a panel of solid and lymphoblastic cancer cells. Our results demonstrate that in contrast to laxaphycin A, laxaphycin B inhibits the proliferation of sensitive and resistant human cancer cell lines and that this activity is strongly increased in the presence of laxaphycin A. This effect appears to be due to an unusual biological synergism.

An intermediate in a new synthesis approach to beta-substituted beta-hydroxyaspartame.

The crystal and molecular structure of 1-tert-butyl 4-ethyl (2'R,3'R,5'R,2S,3S)-3-bromomethyl-3-hydroxy-2-[(2'-hydroxy-2',6',6'-trimethylbicyclo[3.1.1]hept-3'-ylidene)amino]succinate, C(21)H(34)BrNO(6), is presented. This compound is an intermediate in the new synthetic route to beta-substituted beta-hydroxyaspartates, which are blockers of glutamate transport.

Optically pure beta-substituted beta-hydroxy aspartates as glutamate transporter blockers.

A short asymmetric synthesis of optically pure beta-substituted beta-hydroxy aspartates is described. The key step is an aldol reaction between a glycine enolate derived from an oxazinone intermediate used as chiral auxiliary and various alpha-keto esters. Excellent diastereomeric excesses are obtained.