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Electrochemical Sulfonylation of Lysine Residues in Continuous Flow Microreactors.

Project description

A microreactor for novel peptide functionalisation could spur greener drug discovery

Site-selective modification of proteins or peptides has become a very common strategy to modulate protein function. Addition of a sulfonyl group to lysine, an amino acid that is a constituent of most proteins, is of growing interest to the research community as it could open the door to new possibilities for targeted therapies. Electrosynthesis, particularly for oxidation-reduction reactions involving electron transfer between species, has gained renewed attention as a greener synthesis method within the energy-intensive chemical industry. ELECTROSULF is exploiting the technology in a flow microreactor for oxidative sulfonylation of lysine, creating a new eco-friendly way to functionalise peptides and spur new drug discovery.

Objective

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.

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Topic(s)

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Funding Scheme

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MSCA-IF-EF-ST - Standard EF

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Call for proposal

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(opens in new window) H2020-MSCA-IF-2018

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Coordinator

TECHNISCHE UNIVERSITEIT EINDHOVEN
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 175 572,48
Address
GROENE LOPER 3
5612 AE Eindhoven
Netherlands

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Region
Zuid-Nederland Noord-Brabant Zuidoost-Noord-Brabant
Activity type
Higher or Secondary Education Establishments
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 175 572,48
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