Anca PETER
Sylvia ARPICCO
Synthèse de Nouveaux Dérivés de Cyclodextrines Assistée par l’Intelligence Artificielle
Profil recherché : Master 2/ingénieur en chimie, avec une expérience en chimie organique ou chimie supramoléculaire. - forte motivation à la fois pour la synthèse organique et la caractérisation physico-chimique des molécules (RMN et SM). Compétences: - bonnes connaissances chimie moléculaire. - maîtrise des techniques de caractérisation des molécules organiques.
Synthèse de nouveau modulateur des Toll Like Receptors pour la modulation de l’inflammation et neuro-inflammation.
Profil recherché : Etre titulaire d’un Master 2 spécialisé en chimie organique,
- Avoir de solides connaissances et autonomie en synthèse organique, sur la recherche bibliographique
(Reaxys), la synthèse multiétape des sucres, la purification et la caractérisation de nouveaux composés
- Faire preuve de dynamisme, d’implication et de motivation pour le sujet
- Etre capable de présenter et rédiger les recherches effectuées, de proposer des pistes de travail
- Thèse sur financement ministériel, un très bon classement en licence et master est nécessaire
Michalska-Walkowiak, J.; Sn Antonio, E.; Coumes, F.; Rieger, J.; Terrasson, V.; Pourceau, G.; Wadouachi, A.; Jeux, V.
Finding and developing new biosourced materials that can compete with the current petro-sourced ones are a top priority in order to transition to a more sustainable society. Although the preparation of biosourced polyesters or polyamides is quite well described, finding biosourced and sustainable alternatives to petro-sourced polystyrene is still challenging. Herein, we report the synthesis of polystyrenes prepared in three steps from vanillin, 4-hydrobenzaldehyde, and syringaldehyde, compounds that can be obtained through lignin depolymerization under oxidative conditions. The synthesis involves the conversion of these biosourced platforms into polymerizable styrene derivatives through a methylation of the hydroxyl group followed by an olefination of the aldehyde function. The monomers were first synthesized under conventional conditions using solvents. Then, the synthesis was improved from the sustainability point of view by using a ball mill under solventless conditions, generating much less waste in the process. The three monomers were then converted into biosourced homopolymers through free radical polymerization in bulk, providing functional polystyrene derivatives with thermal properties comparable to those of common petro-sourced polystyrene.
Khanchouch, T.; Vallin, A.; Alali, U.; Benazza, M.; Abidi, R.; Bonnet, V.
Abstract Type 2 diabetes mellitus is a metabolic dreadful disease caused by an uncontrolled glucose level in the bloodstream, particularly high after a meal. Inhibitors of glucosidases, involved in the digestion of carbohydrates, can regulate this post-prandial increase in glucose concentration. The traditional drugs act as competitive inhibitors of both pancreatic α-amylase and α-glucosidases and this unselective inhibition is behind severe gastrointestinal side effects related to the concomitant inhibition of α-amylase. We described herein some perglycosylated cyclodextrins as efficient and selective inhibitors of α-glucosidase with low micromolar IC50 (3.64-7.98 μM) compared to the acarbose (IC50 212 μM), clinically used for patients suffering from type 2 diabetes. On the other hand, they do not inhibit α-amylase (IC50>500 μM). Structure/activity relationship rationalization suggests multiple interactions between the described inhibitors and α-glucosidase, which support the existence of both active site and allosteric interactions.
Synthèse de matériaux multifonctionnels basés sur les carbohydrates pour le développement de l’énergie durable, la santé et l’environnement
Profil recherché : Titulaire d’un Master en chimie organique ou en chimie des matériaux. Connaissances indispensables en caractérisation de molécules (RMN, spectrscopie, etc.). 1) Gout pour l’expérimentation 2) Travail en équipe 3) Rigueur et soin expérimental et dans le traitement des données 4) Maîtrise de l'anglais lu, écrit et parlé 5) Aptitudes rédactionnelles et orales français/anglais
Synthèse de matériaux fonctionnels basés sur les carbohydrates pour le développement de l’énergie durable, la santé et l’environnement
Profil recherché : Titulaire d’un Master en chimie organique ou en chimie des matériaux. Connaissances indispensables en caractérisation de molécules (RMN, spectrscopie, etc.). 1) Gout pour l’expérimentation 2) Travail en équipe 3) Rigueur et soin expérimental et dans le traitement des données 4) Maîtrise de l'anglais lu, écrit et parlé 5) Aptitudes rédactionnelles et orales français/anglais
Chercheur récompensé : Jamal EL-ABID
Encadrement : Dr. Vincent CHAGNAULT et Prof. José KOVENSKY
Résumé vulgarisé: Les oligosaccharides sulfatés sont de petites molécules importantes dans divers processus biologiques. Leur efficacité dépend beaucoup du nombre de groupes sulfate qu'ils contiennent et de leur répartition le long de la molécule. Cependant, il est difficile de fabriquer ces molécules, ce qui limite leur utilisation.
C'est pourquoi il est essentiel de rechercher des alternatives. Par exemple, nous avons développé une nouvelle méthode pour créer des molécules similaires aux oligosaccharides sulfatés en remplaçant les groupes sulfate par des groupes sulfonate plus stables en utilisant une méthode plus éco-compatible.
Nous avons ensuite testé ces nouvelles molécules pour voir comment elles interagissent avec certaines protéines et comment elles affectent l'inflammation. Il s'est avéré que l'une de ces molécules est plus efficace pour activer une protéine impliquée dans l'inflammation que son équivalent sulfaté. De plus, une autre molécule s'est révélée être un inhibiteur prometteur d'une enzyme liée à la coagulation sanguine.
En résumé, notre travail vise à créer des molécules similaires aux oligosaccharides sulfatés et à explorer leurs applications potentielles dans le domaine de la biologie et de la santé.
Ballout, N.; Boullier, A.; Darwiche, W.; Ait-Mohand, K.; Trécherel, E.; Gallégo, T.; Gomila, C.; Yaker, L.; Gennero, I.; Kovensky, J.; Ausseil, J.; Toumieux, S.
Bone fracture healing is a complex biological process involving four phases coordinated over time: hematoma formation, granulation tissue formation, bony callus formation, and bone remodelling. Bone fractures represent a significant health problem, particularly among the elderly population and patients with comorbidities. Therapeutic strategies proposed to treat such fractures include the use of autografts, allografts, and tissue engineering strategies. It has been shown that bone morphogenetic protein 2 (BMP-2) has a therapeutic potential to enhance fracture healing. Despite the clinical efficacy of BMP-2 in osteoinduction and bone repair, adverse side effects and complications have been reported. Therefore, in this in vitro study, we propose the use of a disaccharide compound (DP2) to improve the mineralisation process. We first evaluated the effect of DP2 on primary human osteoblasts (HOb), and then investigated the mechanisms involved. Our findings showed that (i) DP2 improved osteoblast differentiation by inducing alkaline phosphatase activity, osteopontin, and osteocalcin expression; (ii) DP2 induced earlier in vitro mineralisation in HOb cells compared to BMP-2 mainly by earlier activation of Runx2; and (iii) DP2 is internalized in HOb cells and activates the protein kinase C signalling pathway. Consequently, DP2 is a potential therapeutical candidate molecule for bone fracture repair.
Die, R. C.; Fanté, B.; Ambeu-Loko, N. C. M.; Hiebel, M. A.; Vallin, A.; Suzenet, F.; Chagnault, V.
Pyrimidine derivatives are an important class of compounds in medicinal chemistry. In this study, a series of 6-aryl4-oxo-1,4-dihydropyrimidine-5-carbonitrile derivatives were synthesized using a multicomponent reaction, followed by S-alkylation with different halogenated derivatives, and then evaluated for their antibacterial activities. Ciprofloxacin was used as the reference antibiotic. The prepared compounds were characterized by 1H, 13C NMR, FTIR spectroscopy, and LC-and HR-MS spectrometry. All compounds were screened in vitro against Pseudomonas aeruginosa and Escherichia coli (Gram-negative bacteria), as well as Staphylococcus aureus and Enterococcus faecalis (Gram-positive bacteria). The results showed that S-alkylation is beneficial in improving the antibacterial activity of the thiouracil derivatives offering a few compounds with antibacterial activity against Gram-positive bacteria.
Bonnet, V.; Clodic, G.; Sonnendecker, C.; Zimmermann, W.; Przybylski, C.
Cyclic oligosaccharides are well known to interact with various metals, able to form supramolecular complexes with distinct sizes and shapes. However, the presence of various isomers in a sample, including positional isomers and conformers, can significantly impact molecular recognition, encapsulation ability and chemical reactivity. Therefore, it is crucial to have tools for deep samples probing and correlation establishments. The emerging ion mobility mass spectrometry (IM-MS) has the advantages to be rapid and sensitive, but is still in its infancy for the investigation of supramolecular assemblies. In the herein study, it was demonstrated that IM-MS is suitable to discriminate several isomers of cyclodextrins (CD)-metals complexes, used as cyclic oligosaccharide models. In this sense, we investigated branched 6-O-α-glucosyl- or 6-O-α-maltosyl-β-cyclodextrins (G1-β-CD and G2-β-CD) and their purely cyclic isomers: CD8 (γ-CD) and CD9 (δ-CD). The corresponding collision cross section (CCS) values were deducted for the main positive singly and doubly charged species. Experimental CCS values were matched with models obtained from molecular modelling. The high mobility resolving power and resolution enabled discrimination of positional isomers, identification of various conformers and accurate relative content estimation. These results represent a milestone in the identification of carbohydrate conformers that cannot be easily reached by other approaches.
