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

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Project 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.

Original text from CORDIS.

Participants

• UNIVERZITA PALACKEHO V OLOMOUCI · OlomoucCoordinatorCzechia
• THE UNIVERSITY COURT OF THE UNIVERSITY OF ST ANDREWS · ST ANDREWSUnited Kingdom

Links

• View on CORDIS
• DOI: 10.3030/101278303