Valérie Rolland

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. The aim of this review is to overview the latest updates in the domain of peptide neurotoxins that affect voltage-gated calcium channels, with a special focus on ω-agatoxins.

Glutamate transporter blockers: enantiomerically pure (2S,3S)- and (2S,3R)-3-methyl glutamic acids

Abstract A short four-step synthesis of (2S,3R)- and (2S,3S)-3-methyl glutamic acids is reported; the (2S,3R) isomer presented a significant inhibitory effect on glutamate transport.

Optically pure β-substituted β-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.

Synthesis, resolution, and determination of absolute configuration of protected α-ethynylphenylalanine enantiomers

Racemic-protected α-ethynylphenylalanine was synthesized from dl-2-benzylserine using α-benzylserinal as key intermediate and was successfully resolved by HPLC on a chiral stationary phase at a semipreparative scale. The absolute configuration of both enantiomers was determined by vibrational circular dichroism.

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.

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. New efficient chemoenzymatic preparations of those compounds using α-chymotrypsin (α-CT) are presented.

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...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-hy­droxy-3-(4-methyl­benzene­sulfonamido)­succinate

The asymmetric unit of the title compound, C17H25NO7S, contains two independent molecules, which are enantiomers forming a hydrogen-bonded dimer associated with two R 2 2(7) patterns. In each molecule, one ethyl group from the two available ethyl ester functional groups is disordered. In one molecule, the ethyl group of the ester function from an α-carboxylic acid is positionally disordered over two sets of sites with occupancies of 0.66:0.34. In the second molecule, 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.