Descrizione del progetto
Un microreattore per una nuova funzionalizzazione dei peptidi potrebbe incentivare una scoperta di farmaci più ecologica
La modifica sito-selettiva di proteine o peptidi è diventata una strategia molto comune per modulare la funzione delle proteine. L’aggiunta di un gruppo solfonilico alla lisina, un aminoacido che compone gran parte delle proteine, è di crescente interesse per la comunità di ricerca in quanto potrebbe aprire le porte a nuove possibilità per terapie mirate. L’elettrosintesi, in particolare per le reazioni di ossido-riduzione che implicano il trasferimento di elettroni tra le specie, ha acquisito una rinnovata attenzione come metodo di sintesi più ecologico nell’industria chimica ad alta intensità energetica. ELECTROSULF sta sfruttando la tecnologia in un microreattore a flusso per la solfonilazione ossidativa della lisina, creando un nuovo modo ecologico per funzionalizzare peptidi e stimolare la scoperta di nuovi farmaci.
Obiettivo
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.
Campo scientifico
- natural scienceschemical sciencescatalysisphotocatalysis
- natural scienceschemical scienceselectrochemistryelectrolysis
- natural sciencesbiological sciencesbiochemistrybiomolecules
- social scienceseconomics and businessbusiness and managementemployment
- natural scienceschemical sciencesorganic chemistryamines
Programma(i)
Argomento(i)
Meccanismo di finanziamento
MSCA-IF-EF-ST - Standard EFCoordinatore
5612 AE Eindhoven
Paesi Bassi