Descripción del proyecto
Un microrreactor para funcionalizar péptidos nuevos podría estimular el descubrimiento de fármacos más ecológicos
La modificación selectiva con el sitio de proteínas o péptidos se ha convertido en una estrategia muy habitual para modular la función proteica. Añadir un grupo sulfonilo a la lisina, un aminoácido que integra la mayoría de las proteínas, suscita un interés creciente en la comunidad investigadora, ya que podría abrir la puerta a nuevas posibilidades de terapias dirigidas. La electrosíntesis, en particular, en las reacciones de reducción-oxidación en las que se produce la transferencia de electrones entre especies, ha suscitado un interés renovado como método de síntesis más ecológico dentro de la industria química de alto consumo energético. ELECTROSULF aprovecha esta tecnología en un microrreactor de flujo para la sulfonación oxidativa de la lisina, y crea una nueva forma respetuosa con el medio ambiente de funcionalizar los péptidos y estimular el descubrimiento de fármacos nuevos.
Objetivo
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.
Ámbito científico
- natural scienceschemical sciencescatalysisphotocatalysis
- natural scienceschemical scienceselectrochemistryelectrolysis
- natural sciencesbiological sciencesbiochemistrybiomolecules
- social scienceseconomics and businessbusiness and managementemployment
- natural scienceschemical sciencesorganic chemistryamines
Programa(s)
Régimen de financiación
MSCA-IF-EF-ST - Standard EFCoordinador
5612 AE Eindhoven
Países Bajos