Description du projet
Un microréacteur destiné à la fonctionnalisation innovante des peptides pourrait encourager une découverte de médicaments plus écologique
La modification sélective de protéines ou de peptides est devenue une stratégie très fréquente pour moduler la fonction protéique. L’addition d’un groupe sulfuryle à la lysine, un acide aminé qui compose la plupart des protéines, suscite de plus en plus d’intérêt au sein de la communauté de la recherche, car il pourrait ouvrir la porte à de nouvelles possibilités en matière de traitements ciblés. L’électrosynthèse, notamment pour les réactions d’oxydoréduction impliquant le transfert d’électrons entre espèces, fait l’objet d’une attention renouvelée comme méthode de synthèse plus écologique au sein de l’industrie chimique à forte intensité énergétique. ELECTROSULF exploite la technologie d’un microréacteur à flux pour la sulfonylation oxydative de la lysine, créant ainsi une nouvelle façon respectueuse de l’environnement de fonctionnaliser des peptides et stimulant une nouvelle découverte de médicaments.
Objectif
Peptides are important molecules, ubiquitous in biological systems. Their relevance in the pharmaceutical sector is proven by the constant increase which the global market of peptide-based drugs is experiencing in the last years. As a consequence, several methods have been developed to modify peptides (e.g. condensation, cross-coupling, transition-metal catalysis, and photocatalysis), being lysine with its free amine one of the most preferred handles used by chemists to introduce a new moieties, e.g. cytotoxic drugs or fluorescent labels. Several transformations as alkylation, arylation, oxidation, acylation and condensation have been described for lysine. However, it would be very appealing to introduce selectively a sulfonyl group, which would result in the formation of a sulfonamide, a functionality which is widely employed in drugs. Although several oxidative sulfonylations are reported in the literature, their drawbacks motivate me to look for greener synthetic strategies. Electrosynthesis represents an advantageous alternative, which has been re-discovered in the last years also thanks to its employment in continuous-flow microreactors. With the support of this modern technology, it is possible to minimize the difficulties connected to older electrochemical processes (such as mass-transfer limitation, the need of a supporting electrolyte,and the difficult scale-up). ELECTROSULF aims at developing a novel sulfonylation of lysine by electrochemical means with the use of a flow microreactor. The reaction mechanism will be also properly studied. My strong background in organic chemistry together with Prof. Timothy Noël’s expertise in flow processes and reaction miniaturization will guarantee the success of ELECTROSULF, whose achievement will have a great impact on the pharmaceutical sector, paving the path to a new approach for peptide modification.
Champ scientifique
- natural scienceschemical sciencescatalysisphotocatalysis
- natural scienceschemical scienceselectrochemistryelectrolysis
- natural sciencesbiological sciencesbiochemistrybiomolecules
- social scienceseconomics and businessbusiness and managementemployment
- natural scienceschemical sciencesorganic chemistryamines
Programme(s)
Régime de financement
MSCA-IF-EF-ST - Standard EFCoordinateur
5612 AE Eindhoven
Pays-Bas