La RMN, un outil pour la métabolomique

International audienc

Isis cumulative bibliography 1966-1975, a bibliography of the history of science formed from Isis critical bibliographies 91-100 indexing literature published from 1965 through 1974, edited by John Neu, II, Subjects, periods and civilizations. London, New York : Mansell, History of science society, 1985. in-4°, VII-711 pages.

Poulle Emmanuel. Isis cumulative bibliography 1966-1975, a bibliography of the history of science formed from Isis critical bibliographies 91-100 indexing literature published from 1965 through 1974, edited by John Neu, II, Subjects, periods and civilizations. London, New York : Mansell, History of science society, 1985. in-4°, VII-711 pages.. In: Bibliothèque de l'école des chartes. 1985, tome 143, livraison 2. p. 475

NMR metabolimics to detect Huntington’s disease at early stage

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Metabolomic NMR studies at presymptomatic and symptomatic stages of Huntington’s disease, on drosophila model

International audienc

Solution structures of stomoxyn and spinigerin, two insect antimicrobial peptides with an alpha-helical conformation

Stomoxyn and spinigerin belong to the class of linear cysteine-free insect antimicrobial peptides that kill a range of microorganisms, parasites, and some viruses but without any lytic activity against mammalian erythrocytes. Stomoxyn is localized in the gut epithelium of the nonvector stable fly that is sympatric with the trypanosome vector tsetse fly. Spinigerin is stored and secreted by hemocytes from the fungus-growing termite. The structure of synthetic stomoxyn and spinigerin in aqueous solution and in TFE/water mixtures was analyzed by CD and NMR spectroscopy combined with molecular modeling calculations. Stomoxyn and spinigerin adopt a flexible random coil structure in water while both assume a stable helical structure in the presence of TFE. In 50% TFE, the structure of stomoxyn is typical of cecropins, including an amphipathic helix at the N-terminus and a hydrophobic C-terminus with helical features that probably fold in a helical conformation at higher TFE concentration. In contrast to stomoxyn, spinigerin acquires very rapidly a helical conformation. In 10% TFE the helix is highly bent and the structure is poorly defined. In 50% TFE, the helical structure is well defined all along its sequence, and the slightly bent -helix displays an amphiphilic character, as observed for magainin 2. The structural similarities between stomoxyn and cecropin A from Hyalophora cecropia and between spinigerin and magainin 2 suggest a similar mode of action on the bacterial membranes of both pairs of peptides. Our results also confirm that TFE induces helix formation and propagation for amino acids showing helical propensity in water but also enhances the helix propagation propensity of nonpolar -branched residues

Investigation of the structural parameters involved in the delta-opioid selectivity of several families of opioid peptides.

International audienceThree series of highly delta-opioid selective peptides are now available, and each family is used as template to investigate the structural parameters involved in delta-receptor recognition and in the modulation of the selectivity of the parent peptide. The first series includes cyclic derivatives such as Tyr-D-Pen-Gly-Phe-D-Pen(DPDPE) and Tyr-D-Pen-Gly-Phe-Pen(DPLPE); the second are the synthetic linear constrained peptides [Tyr-D-Ser(OtBu)-Gly-Phe-Leu-Thr(DSTBULET), Tyr-D-Ser(OtBu)-Gly-Phe-Leu-Thr (OtBu)(BUBU) and especially Tyr-D-Cys(StBu)-Gly-Phe-Leu-Thr(OtBu) (BUBUC)] and the last one the natural peptides [Tyr-D-Met-Phe-His-Leu-Met-Asp-NH2 (deltorphin or dermenkephalin) and Tyr-D-Ala-Phe-Asp-Val-Val-GlyNH2 ([D-Ala2] deltorphin I)]. In the present study, the possibly of transposing some of the decisive factors of delta-selectivity evidenced in the two other families, to the linear constrained peptides series was examined. With this aim in view, residues such as Phe3, pClPhe4 or Asp were introduced in the sequence of DSTBULET, BUBU or BUBUC. Direct comparison between the biochemical profiles of the [pClPhe4] analogs of the linear constrained peptides and their parent compounds shows that the addition of an electronegative atom on the Phe4 residue of enkephalin sequences is not an absolute parameter for delta-selectivity improvement. The hydrophobic delta-receptor subsite seems able to receive a range of molecular volumes and electronegativities. By contrast, this subsite cannot interact with a Phe3 aromatic ring introduced in this series of peptides. Moreover, the results obtained with linear peptides including additional negatively charged residues demonstrate that the proposed location of the delta-receptors in a cationic membrane environment is not adequate to explain the selectivity profile of a number of compounds

Investigation of the structural parameters involved in the delta-opioid selectivity of several families of opioid peptides.

International audienceThree series of highly delta-opioid selective peptides are now available, and each family is used as template to investigate the structural parameters involved in delta-receptor recognition and in the modulation of the selectivity of the parent peptide. The first series includes cyclic derivatives such as Tyr-D-Pen-Gly-Phe-D-Pen(DPDPE) and Tyr-D-Pen-Gly-Phe-Pen(DPLPE); the second are the synthetic linear constrained peptides [Tyr-D-Ser(OtBu)-Gly-Phe-Leu-Thr(DSTBULET), Tyr-D-Ser(OtBu)-Gly-Phe-Leu-Thr (OtBu)(BUBU) and especially Tyr-D-Cys(StBu)-Gly-Phe-Leu-Thr(OtBu) (BUBUC)] and the last one the natural peptides [Tyr-D-Met-Phe-His-Leu-Met-Asp-NH2 (deltorphin or dermenkephalin) and Tyr-D-Ala-Phe-Asp-Val-Val-GlyNH2 ([D-Ala2] deltorphin I)]. In the present study, the possibly of transposing some of the decisive factors of delta-selectivity evidenced in the two other families, to the linear constrained peptides series was examined. With this aim in view, residues such as Phe3, pClPhe4 or Asp were introduced in the sequence of DSTBULET, BUBU or BUBUC. Direct comparison between the biochemical profiles of the [pClPhe4] analogs of the linear constrained peptides and their parent compounds shows that the addition of an electronegative atom on the Phe4 residue of enkephalin sequences is not an absolute parameter for delta-selectivity improvement. The hydrophobic delta-receptor subsite seems able to receive a range of molecular volumes and electronegativities. By contrast, this subsite cannot interact with a Phe3 aromatic ring introduced in this series of peptides. Moreover, the results obtained with linear peptides including additional negatively charged residues demonstrate that the proposed location of the delta-receptors in a cationic membrane environment is not adequate to explain the selectivity profile of a number of compounds

Metabolomic NMR studies & Huntington’s disease: models in transgenic drosophila

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Metabolomic NMR studies at presymptomatic and symptomatic stages of Huntington’s disease, on drosophila model

International audienc

Huntington’s disease: metabolomic studies by NMR analyzes on Drosophila Model

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