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Neier, Reinhard

Nom
Neier, Reinhard
Affiliation principale
Fonction
Professeure ordinaire
Email
Reinhard.Neier@unine.ch
Identifiants
https://libra.unine.ch/handle/123456789/383
_
0000-0003-0890-1797

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  • Publication
    Métadonnées seulement
    Structure of yeast 5-aminolevulinic acid dehydratase complexed with the inhibitor 5-hydroxylevulinic acid
    (2005)
    Erskine, P. T.
    ;
    Coates, L.
    ;
    Newbold, R.
    ;
    Brindley, A. A.
    ;
    Stauffer, Frederic
    ;
    Beaven, G. D. E.
    ;
    Gill, R.
    ;
    Coker, A.
    ;
    Wood, S. P.
    ;
    Warren, M. J.
    ;
    Shoolingin-Jordan, P. M.
    ;
    Neier, Reinhard 
    ;
    Cooper, J. B.
    The x-ray crystal structure of 5-aminolevulinate dehydratase (ALAD) of yeast complexed with the competitive inhibitor, 5-hydroxylevulinic acid, was detd. at a resoln. of 1.9 Ã…. The structure showed that the inhibitor was bound by a Schiff-base link to one of the invariant active site Lys residues (Lys-263). The inhibitor appeared to bind in 2 well-defined conformations and the interactions made by it suggested that it is a very close analog of the substrate, 5-aminolevulinic acid (ALA). [on SciFinder(R)]
  • Publication
    Accès libre
    Porphobilinogen Synthase : A Challenge for the Chemist ?
    (2001)
    Stauffer, Frederic
    ;
    Zizzari, Eleonora
    ;
    Soldermann-Pissot, Carole
    ;
    Faurite, Jean-Philippe
    ;
    Neier, Reinhard 
    The initial steps in the biosynthesis of the tetrapyrrolic dyes, called the 'pigments of life', are highly convergent. The formation of porphobilinogen, the pyrrolic precursor of the tetrapyrrolic skeleton, uses δ-aminolevulinate as the starting material. This amino acid is dedicated to the biosynthesis of tetrapyrroles. However, the chemical condensation of δ-aminolevulinate leads to a symmetric pyrazine. Attempts to imitate the biosynthesis using one of the proposed pathways for the biosynthesis of porphobilinogen as a guideline has allowed us to synthesize a protected precursor of porphobilinogen in an efficient way. Based on the two major proposals for the biosynthesis, a series of specifically synthesized inhibitors was also tested. The inhibition behavior and the potency of the inhibitors expressed as their Ki value has unraveled an interesting relationship between the structure of the inhibitor and the strength of its interaction with the active site. The concerted use of mechanistic analysis, synthesis and kinetic studies of inhibitors has increased our knowledge about the enzyme porphobilinogen synthase. Structural studies of enzyme-inhibitor complexes will hopefully complement the kinetic results accumulated so far.
  • Publication
    Métadonnées seulement
    Synthesis of Tri- and Tetrasubstituted Furans Catalyzed by Trifluoroacetic Acid
    (2000)
    Stauffer, Frederic
    ;
    Neier, Reinhard 
    Substituted 2-hydroxy-3-acetylfurans are synthesized by alkylation of tert-Bu acetoacetate with an ?-haloketone followed by treatment of the obtained intermediate with trifluoroacetic acid (TFA). A second alkylation of the intermediate followed by treatment with trifluoroacetic acid provides access to disubstituted 2-methylfurans. For example, alkylation of tert-Bu acetoacetate with Me 5-bromolevulinate gave 2-acetyl-4-oxoheptanedioic acid 1-(1,1-dimethylethyl) 7-Me ester. Treatment of the latter with trifluoroacetic acid gave 4-acetyl-5-hydroxy-2-furanpropanoic acid Me ester. [on SciFinder(R)]
  • Publication
    Métadonnées seulement
    Inhibition of porphobilinogen synthase (PBG-synthase) by 4,6-dioxoheptanoic acid and related compounds
    (1998)
    Stauffer, Frederic
    ;
    Jarret, Caroline
    ;
    Engeloch, Thomas
    ;
    Henz, Matthias
    ;
    Bobalova, Janette
    ;
    Neier, Reinhard 
    We are investigating the mechanism of PBG-synthase by active site directed inhibition studies. The procedure for testing and the data obtained with compds. related to 4,6-dioxoheptanoic acid are reported and the results are discussed in the context of our kinetic model. [on SciFinder(R)]