Chemo-enzymatic synthesis of pseudo-glyo-amino acids, analogues of sialyl Lewis x antigen
This thesis deals with the chemoenzymatic synthesis of pseudoglycosyl amino acid building-blocks carrying the sialyl Lewis x antigen (sLex), where the sialic acid is replaced by a succinic ester as a substitute for the carboxylate function involved in selectin/sLex interaction. These compounds could...
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2009
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ftunivnantes:oai:HAL:tel-03520765v1 2023-05-15T14:15:43+02:00 Chemo-enzymatic synthesis of pseudo-glyo-amino acids, analogues of sialyl Lewis x antigen Synthèse chimio-enzymatique de pseudo-glyco-aminoacides, analogues de l'antigène Lewis x sialylé Bridiau, Nicolas LIttoral ENvironnement et Sociétés (LIENSs) La Rochelle Université (ULR)-Centre National de la Recherche Scientifique (CNRS) Université de La Rochelle Thierry Maugard 2009-05-07 https://hal.science/tel-03520765 fr fre HAL CCSD tel-03520765 https://hal.science/tel-03520765 https://hal.science/tel-03520765 Biochimie, Biologie Moléculaire. Université de La Rochelle, 2009. Français. ⟨NNT : ⟩ Metastase Selectines Hydrolases CAZY Maillard reaction Métastases Sélectines Réaction Maillard [SDV.BBM]Life Sciences [q-bio]/Biochemistry Molecular Biology [CHIM.ORGA]Chemical Sciences/Organic chemistry info:eu-repo/semantics/doctoralThesis Theses 2009 ftunivnantes 2023-03-08T02:14:07Z This thesis deals with the chemoenzymatic synthesis of pseudoglycosyl amino acid building-blocks carrying the sialyl Lewis x antigen (sLex), where the sialic acid is replaced by a succinic ester as a substitute for the carboxylate function involved in selectin/sLex interaction. These compounds could potentially act as antimetastatic inhibitors of endothelial vascular cell/malignant tumor cell interactions. The work is broken down into four parts. The first one consists in the study of N- and pseudo-C-glycosylation of aromatic amines by Maillard reaction, which allowed to obtain the worthwhile products β-N-acetyl-D-glucosaminyl- and β-N-lactosaminyl-p-aminophenylalanine as well as the Amadori compound N-[β-D-galactosyl-1,4-(1-deoxyfructos-1-yl)]-p-aminophenylalanine. The second part describes the synthesis of N-acetyl-lactosamine (LacNAc) by transgalactosylation of the N-acetyl-D-glucosamine (GlcNAc), catalysed in aqueous and hydro-organic media by the β-galactosidases of Kluyveromyces lactis and Bacillus circulans. The third part mainly reports the search for α-L-transfucosidases activities by screening of various commercial enzymatic preparations of glycosidases in parallel with the use of two α-L-fucosidases of Thermotoga maritima, the wild type and its P25 mutant obtained by directed evolution, for the enzymatic synthesis of αFuc-1,3-GlcNAc, in aqueous and hydro-organic media. Eventually in the last part, our focus is on the succinic anhydride condensation on LacNAc, catalysed by the Candida antartica lipase B in anhydrous organic medium, which led to the formation of the desired mono-, di- and tri-succinylated LacNAc derivatives. Cette thèse a pour objet la synthèse chimio-enzymatique de pseudo-glyco-aminoacides portant une structure analogue de l’antigène Lewis x sialylé (sLex) où l’acide sialique est remplacé par un ester succinique mimant la fonction carboxylate impliquée dans l’interaction sélectine/sLex. Ces composés pourraient jouer le rôle d’inhibiteurs d’interactions cellule endothéliale ... Doctoral or Postdoctoral Thesis antartic* Université de Nantes: HAL-UNIV-NANTES |
institution |
Open Polar |
collection |
Université de Nantes: HAL-UNIV-NANTES |
op_collection_id |
ftunivnantes |
language |
French |
topic |
Metastase Selectines Hydrolases CAZY Maillard reaction Métastases Sélectines Réaction Maillard [SDV.BBM]Life Sciences [q-bio]/Biochemistry Molecular Biology [CHIM.ORGA]Chemical Sciences/Organic chemistry |
spellingShingle |
Metastase Selectines Hydrolases CAZY Maillard reaction Métastases Sélectines Réaction Maillard [SDV.BBM]Life Sciences [q-bio]/Biochemistry Molecular Biology [CHIM.ORGA]Chemical Sciences/Organic chemistry Bridiau, Nicolas Chemo-enzymatic synthesis of pseudo-glyo-amino acids, analogues of sialyl Lewis x antigen |
topic_facet |
Metastase Selectines Hydrolases CAZY Maillard reaction Métastases Sélectines Réaction Maillard [SDV.BBM]Life Sciences [q-bio]/Biochemistry Molecular Biology [CHIM.ORGA]Chemical Sciences/Organic chemistry |
description |
This thesis deals with the chemoenzymatic synthesis of pseudoglycosyl amino acid building-blocks carrying the sialyl Lewis x antigen (sLex), where the sialic acid is replaced by a succinic ester as a substitute for the carboxylate function involved in selectin/sLex interaction. These compounds could potentially act as antimetastatic inhibitors of endothelial vascular cell/malignant tumor cell interactions. The work is broken down into four parts. The first one consists in the study of N- and pseudo-C-glycosylation of aromatic amines by Maillard reaction, which allowed to obtain the worthwhile products β-N-acetyl-D-glucosaminyl- and β-N-lactosaminyl-p-aminophenylalanine as well as the Amadori compound N-[β-D-galactosyl-1,4-(1-deoxyfructos-1-yl)]-p-aminophenylalanine. The second part describes the synthesis of N-acetyl-lactosamine (LacNAc) by transgalactosylation of the N-acetyl-D-glucosamine (GlcNAc), catalysed in aqueous and hydro-organic media by the β-galactosidases of Kluyveromyces lactis and Bacillus circulans. The third part mainly reports the search for α-L-transfucosidases activities by screening of various commercial enzymatic preparations of glycosidases in parallel with the use of two α-L-fucosidases of Thermotoga maritima, the wild type and its P25 mutant obtained by directed evolution, for the enzymatic synthesis of αFuc-1,3-GlcNAc, in aqueous and hydro-organic media. Eventually in the last part, our focus is on the succinic anhydride condensation on LacNAc, catalysed by the Candida antartica lipase B in anhydrous organic medium, which led to the formation of the desired mono-, di- and tri-succinylated LacNAc derivatives. Cette thèse a pour objet la synthèse chimio-enzymatique de pseudo-glyco-aminoacides portant une structure analogue de l’antigène Lewis x sialylé (sLex) où l’acide sialique est remplacé par un ester succinique mimant la fonction carboxylate impliquée dans l’interaction sélectine/sLex. Ces composés pourraient jouer le rôle d’inhibiteurs d’interactions cellule endothéliale ... |
author2 |
LIttoral ENvironnement et Sociétés (LIENSs) La Rochelle Université (ULR)-Centre National de la Recherche Scientifique (CNRS) Université de La Rochelle Thierry Maugard |
format |
Doctoral or Postdoctoral Thesis |
author |
Bridiau, Nicolas |
author_facet |
Bridiau, Nicolas |
author_sort |
Bridiau, Nicolas |
title |
Chemo-enzymatic synthesis of pseudo-glyo-amino acids, analogues of sialyl Lewis x antigen |
title_short |
Chemo-enzymatic synthesis of pseudo-glyo-amino acids, analogues of sialyl Lewis x antigen |
title_full |
Chemo-enzymatic synthesis of pseudo-glyo-amino acids, analogues of sialyl Lewis x antigen |
title_fullStr |
Chemo-enzymatic synthesis of pseudo-glyo-amino acids, analogues of sialyl Lewis x antigen |
title_full_unstemmed |
Chemo-enzymatic synthesis of pseudo-glyo-amino acids, analogues of sialyl Lewis x antigen |
title_sort |
chemo-enzymatic synthesis of pseudo-glyo-amino acids, analogues of sialyl lewis x antigen |
publisher |
HAL CCSD |
publishDate |
2009 |
url |
https://hal.science/tel-03520765 |
genre |
antartic* |
genre_facet |
antartic* |
op_source |
https://hal.science/tel-03520765 Biochimie, Biologie Moléculaire. Université de La Rochelle, 2009. Français. ⟨NNT : ⟩ |
op_relation |
tel-03520765 https://hal.science/tel-03520765 |
_version_ |
1766288024975441920 |