The Glutathione Metabolite γ-Glutamyl-Glutamate Partially Activates Glutamate NMDA Receptors in Central Neurons With Higher Efficacy for GluN2B-Containing Receptors.

Gamma-L-glutamyl-L-glutamate (γ-Glu-Glu) was synthetized and further characterized for its activity on cultured neurons. We observed that γ-Glu-Glu elicited excitatory effects on neurons likely by activating mainly the N-methyl-D-aspartate (NMDA) receptors. These effects were dependent on the integrity of synaptic transmission as they were blocked by tetrodotoxin (TTX).

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.

Synthesis and characterization of a cyclooctapeptide analogue of ω-agatoxin IVB enhancing the activity of Cav2.1 calcium channels activity in cultured hippocampal neurons.

The structure of the toxin ω-agatoxin IVB, extracted from the venom of funnel-web spider Agelenopsis aperta, is an important lead structure when considering the design of modulators of synaptic transmission which largely involves P/Q-type (CaV2.1) voltage gated calcium channels (VGCC) at central synapses. Focusing on the loop 2 of the ω-agatoxin IVB that seems to be the most preeminent interacting domain of the toxin with the CaV2.

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.

Peptide neurotoxins that affect voltage-gated calcium channels: a close-up on ω-agatoxins.

Peptide neurotoxins found in animal venoms have gained great interest in the field of neurotransmission. As they are high affinity ligands for calcium, potassium and sodium channels, they have become useful tools for studying channel structure and activity. Peptide neurotoxins represent the clinical potential of ion-channel modulators across several therapeutic fields, especially in developing new strategies for treatment of ion channel-related diseases.

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

Two concomitant polymorphs, (I) and (II), of a β-benzyl-β-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.

Chemoenzymatic routes to enantiomerically pure 2-azatyrosine and 2-, 3- and 4-pyridylalanine derivatives.

Enantiomerically pure 2-, 3- or 4-pyridylalanine (pya) and 2-azatyrosine (azatyr) are known to present various biological activities. After incorporation into appropriate peptide sequences, these heterocyclic non natural α-amino acids could behave as new substrates or inhibitors of elastase from Pseudomonas aeruginosa. This enzyme is known to be involved in nosocomial infections and infections related to the cystic fibrosis disease.

Synthesis of cyclooctapeptides: constraints analogues of the peptidic neurotoxin, omega-agatoxine IVB-an experimental point of view.

omega-AGA IVB is an important lead structure when considering the design of effectors of glutamate release inducting P/Q-type calcium channels. The best route to achieve the analogues possessing the three-dimensional arrangement corresponding to the native binding loop was the introduction of constraint by ring formation via side chain to side chain lactamization for suitably protected Lys and Glu residues. Since tryptophane residue located at position 14 of this neuropeptide has been suggested as essential for binding, analogues in which this amino acid was replaced by aza-tryptophane and alanine were synthesized.

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.

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.

Vitamins and minerals: a model for safe addition to foods.

Background: Significant subgroups in most European populations have intakes below nationally recommended levels for several vitamins, minerals and trace elements, placing individuals at risk of suboptimal intake of important vitamins and minerals. The voluntary addition of micronutrients to the appropriate foods may help address the risks associated with low micronutrient intakes. However, concerns need to be addressed regarding the potential for unacceptably high intakes, particularly for those people consuming very large amounts of food.

Body weight, body composition, and energy metabolism in lean and obese Zucker rats fed soybean oil or butter.

Background: Dietary fat composition is thought to affect body weight regulation independent of the amount of fat ingested.

Objective: We analyzed the feeding behavior, body weight gain, body composition, and energy metabolism in lean and obese rats fed a diet in which fat was in the form of either butter or soybean oil.

Design: Ten lean (Fa/?) and 10 obese (fa/fa) adult Zucker rats were divided into 4 groups according to a 2 x 2 experimental design.