Metal-based Photoimmunotherapy Agents for the Targeted Treatment of Neuroblastoma Primary supervisor: Adam Sedgwick, King's College London Secondary supervisor: Jeannine Hess, The Francis Crick Ins...

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Metal complexes offer unique opportunities as scaffolds in chemical biology and drug discovery, with tuneable geometry, modular coordination environments, and structural features not readily accessibl...

Here we report a C3-symmetric metal-binding tripeptide, BTMA-1, that self-assembles in water into either a chiral supramolecular helical polymer or a discrete CoII peptide helicate, depending on metal coordination. The CoII peptide helicate exhibits high affinity and selectivity toward DNA three-way junctions (3WJ), a class of noncanonical DNA structures with emerging biological relevance. Importantly, we demonstrate that the recognition process can be triggered dynamically by adding CoII ions to a dispersion of the supramolecular polymer, which acts as an inert precursor reservoir in physiological media. In this way, our strategy shows that chiral supramolecular helical polymers can form temporarily inactive aggregates that release discrete helicates for biomolecular recognition, such as 3WJ binding, upon metal ion coordination. Overall, this mechanism reveals a previously unexplored capability of this class of materials and offers a new approach for the design of responsive supramolecular systems for nucleic acid recognition and anticancer therapy.

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