Vignette d'image

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

Résultat de la recherche

Filtres

3
3
Réinitialiser les filtres

Paramètres

Voici les éléments 1 - 3 sur 3
  • 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
    Accès libre
    A Biomimetic Synthesis of a Porphobilinogen Precursor Using a Mukaiyama Aldol Reaction
    (1998)
    Chaperon, André
    ;
    Engeloch, Thomas M.
    ;
    Neier, Reinhard 
    Four steps suffice! A protected porphobilinogen was obtained in 25 % yield in a straightforward synthesis starting from a derivative of 5-aminolevulinate. The key was the use of a cyanide derivative instead of the azide. The synthesis imitates the mechanism proposed by Shemin for the biosynthesis of porphobilinogen. Phth = phthaloyl.
  • Publication
    Accès libre
    On the formation of the mixed pyrrole catalysed by porphobilinogen synthase from Rhodobacter spheroides
    (1996)
    Lüönd, Rainer Martin
    ;
    Neier, Reinhard 
    The enzyme porphobilinogen synthase (PBGS) catalyses the formation of porphobilinogen (PBG) from two molecules of 5-aminolevulinic acid (ALA). It has been claimed that the PBGS from Rhodobacter spheroides is able to form a mixed pyrrole, from one molecule of 5-aminolevulinic acid and one molecule of levulinic acid. The chemical synthesis of this mixed pyrrole allowed to show, that the compound formed from 5-aminolevulinic acid and levulinic acid with PBGS from R. spheroides has not the proposed structure. The putative enzyme catalysed formation of the mixed pyrrole had been used as an argument for the postulated mechanism of PBGS. In view of our results this line of arguments has to bee re-evaluated.