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Enzyme-integrated high-throughput Multicomponent synthesis for Echo-enabled Rapid molecule generation and Assay in Lead Discovery

Project description

Accelerating drug discovery

Indoles are a class of chemical compounds commonly found in many medicines and natural products, making them highly important in drug discovery. However, methods to efficiently modify and diversify indoles are still limited. With the support of the Marie Skłodowska-Curie Actions programme, the EMERALD project addresses this challenge by developing a miniaturised and automated platform that combines chemical synthesis, enzyme-based modification, and high-throughput screening. This approach enables rapid generation and testing of new indole-based molecules using very small sample volumes and reduced solvent use. By evaluating their activity against a key cancer-related target, the project will demonstrate its strong clinical potential while promoting more sustainable, efficient, and innovative strategies for future drug development.

Objective

Indoles are among the most widely encountered scaffolds in medicines and natural products, yet general strategies for their systematic diversification remain limited. Through EMERALD (Enzyme-integrated high-throughput Multicomponent synthesis for Echo enabled Rapid molecule generation and Assay in Lead Discovery), I will unites three complementary techniques into the first miniaturized, automated pipeline for late-stage indole diversification at nanoliter scale (i) multicomponent reactions for efficient and modular assembly of indole frameworks; (ii) enzymatic tailoring, enabling regio- and chemoselective functionalization; and (iii) acoustic droplet ejection combined with real-time mass spectrometry, delivering ultra-high throughput synthesis and analytics with >90% reductions in solvent use. During a secondment at the University of St Andrews, I will evaluate enzyme panels to produce compatibility and selectivity maps directly relevant to drug discovery. Importantly, a subset of the resulting functionalized indoles will be screened against the p53–MDM2 interaction, a clinically validated target in oncology, to demonstrate the platforms’ direct translational potential. By marrying chemical and enzymatic methodologies, EMERALD establishes a sustainable route to novel scaffolds and natural product–inspired analogues, while providing an ideal interdisciplinary training ground at the interface of chemistry, biocatalysis, and automation-ultimately advancing greener drug discovery and fostering my path to research independence.

Fields of science (EuroSciVoc)

Keywords

Programme(s)

Topic(s)

Funding Scheme

HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships

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Call for proposal

(opens in new window) HORIZON-MSCA-2025-PF

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Coordinator

UNIVERZITA PALACKEHO V OLOMOUCI
Net EU contribution
€ 191 918,16
Address
KRIZKOVSKEHO 8
771 47 Olomouc
Czechia
Region
Česko Střední Morava Olomoucký kraj
Activity type
Higher or Secondary Education Establishments
Links
Total cost
No data

Partners (1)