Synthesis of functional derivative peptides by enzymatic way

• Main Author: Husson, Eric
• Other Authors: Laboratoire des Sciences du Génie Chimique (LSGC), Institut National Polytechnique de Lorraine (INPL)-Centre National de la Recherche Scientifique (CNRS), Institut National Polytechnique de Lorraine, Ivan Marc
• Format: Doctoral or Postdoctoral Thesis
• Language: French
• Published: HAL CCSD 2008
• Subjects: N and/or O-acylation; Supercritical carbon dioxyde; Solvent- free system; Acyl-transferase; Dipeptides; Lipase CAL B; Ionic liquid; Selectivity; Organic solvent; N et/ou O-acylation; Sélectivité; CO2 supercritique; Liquide ionique; Système sans solvant; Solvant organique; Acylation; Peptides; Polyphénols; [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition; [SPI.OTHER]Engineering Sciences [physics]/Other; Antarc*; Antarctica
• Online Access: https://hal.univ-lorraine.fr/tel-01753057; https://hal.univ-lorraine.fr/tel-01753057/document; https://hal.univ-lorraine.fr/tel-01753057/file/2008_HUSSON_E.pdf

The present work consisted in studying the N and/or O-enzymatic acylation of amino alcohols and dipeptides. A preliminary study was firstly undertaken about the enzymatic acylation of a bifunctionnal model molecule, 6-amino-1-hexanol and demonstrated the ability of the lipase B of Candida antarctica to catalyze the acylation of this substrate in different reaction media. The reaction performed in organic solvents (hexane, 2-methyl-2-butanol) allowed to the synthesis of the diacylated product with a substrate conversion yield of 85 %, showing the absence of chimio-selectivity of the reaction. The use of a solvent-free system constituted of free fatty acid and the use of supercritical carbon dioxide permitted to orientate the selectivity of the reaction in favour of the O-acylation. Ionic liquids with imidazolium cation and few nucleophilic anions led to a substrate conversion of 99 % and to maintain the absence of chemo-selectivity observed in organic solvents. Then, the study focused on the acylation of model dipeptides like Lys-Ser, HCl and Ser-Leu. Results relative to the acylation of Lys-Ser, HCl catalyzed by the lipase B of Candida antarctica immobilized showed a selectivity in favour of the acylation of the e-amino function independently of the reaction medium. The Ser-Leu O-acylation permitted to demonstrate the influence of the molecular environment (electro-attractor C terminal carboxylic group) on the reactivity of the serine hydroxyl function. Finally, the enzymatic acylation of a bioactive dipeptide was catalyzed by the lipase B of Candida antarctica immobilized in organic solvent and by the acyl-transferase of Candida parapsilosis in lipid-aqueous biphasic medium. The acylation of carnosine allowed the N-oleyl carnosine synthesis. The acylation of carnosine did not affect its xanthine oxydase inhibition activity and seemed to improve its superoxyde anion scavenging property Ce travail a consisté à étudier la N et/ou O acylation enzymatique d'alcool aminés et de dipeptides.Une étude préliminaire ...