Objectives: Design functionalised scaffolds using MCR chemistry; synthesise medium-sized, structurally diverse libraries biased for PPI/interface engagement; perform iterative SAR cycles (hit-to-lead), scaffold hopping and optimisation of physicochemical and conformational properties; profile all compounds in WP1 TR-FRET and bisubstrate assays under ATP-locking conditions.
Expected results: A rationally assembled small-molecule library, ≥1–2 validated chemotypes with interface-modulating activity and scalable lead compounds suitable for WP4 mechanistic and cellular evaluation.
Secondments: Servier: High-throughput analogue synthesis and hit-refinement support (M20–23; 4 months); GU: Cellular target-engagement and pathway-level validation (M31–33; 3 months).
Integration: Provides binder feed for WP4; tightly linked to WP1 counterscreens and WP2 mechanistic constraints.
Interdisciplinarity: Spans synthetic/medicinal chemistry (MCR scaffolds), chemical biology (assay-guided SAR) and AI-supported design, with translational validation in cell biology
