DÉVELOPEMENT D'UN SYSTÈME DE RÉGÉNÉRATION D'UDP-GA1NAC POUR LA GLYCOSYLATION ENZYMATIQUE D'OLIGOSACCHARIDES ET DE PEPTIDES D'INTÉRÊT THÉRAPEUTIQUE

Abstract : The sugar N-acetylgalactosamine (Ga1NAc) is a constituent of many glycoproteins, glycolipids and proteoglycans. It is the immunodominant sugar in blood group and oncofetal antigens which are potential therapeutic targets. However, the chemical synthesis of these antigens is time consuming and expensive. In vivo, GaINAc is incorporated into glycoconjugates by specific GaINAc transferases using UDPGa1NAc as the donor substrate. At présent, the chemo-enzymatic synthesis of glycans is hampered by the difficulties involved in the synthesis of large amounts of UDPGa1NAc. To overcome these limitations we have developed the chemo-enzymatic synthesis of Ga1NAc bearing glycoconjugates based on the simple substrates Ga1NAc, UTP and creatine-P and the use of four enzymes. In this method UDP-Ga1NAc is synthesized as an intermediate and the product UDP immediately recycled to UDP-Ga1NAc. With this technique an oligosaccharide and several mg of a small glycoprotein were synthesized and the immune response of mice to the synthesized glycoprotein investigated. The system developed to synthesize the UDP-GaINAc intermediate could be adapted to produce large amounts of UDP-Ga1NAc and we could show that it accepts also derivatives of Ga1NAc which allows the rapid synthesis of •UDP-Ga1NAc analogues. These molécules have been tested as probes for the active site of polypeptide aGa1NAc transferase Tl by kinetic studies and by STD-NMR.
Document type :
Theses
Domain :
Complete list of metadatas

Cited literature [216 references]  Display  Hide  Download

https://tel.archives-ouvertes.fr/tel-00160999
Contributor : Patricia Leloup <>
Submitted on : Monday, July 9, 2007 - 4:04:35 PM
Last modification on : Wednesday, June 27, 2018 - 8:24:02 AM
Long-term archiving on : Friday, November 25, 2016 - 6:03:21 PM

Identifiers

  • HAL Id : tel-00160999, version 1

Citation

Vanessa Bourgeau. DÉVELOPEMENT D'UN SYSTÈME DE RÉGÉNÉRATION D'UDP-GA1NAC POUR LA GLYCOSYLATION ENZYMATIQUE D'OLIGOSACCHARIDES ET DE PEPTIDES D'INTÉRÊT THÉRAPEUTIQUE. domain_other. Université d'Orléans, 2006. Français. ⟨tel-00160999⟩

Share

Metrics

Record views

268

Files downloads

1286