Engineering peptide-catecholamine co-assembled nanostructures for tunable fluorescence

Precise engineering of hydrophobic microenvironments in synthetic peptide-catecholamine co-assemblies remains challenging for tunable fluorescence. Hierarchical nanostructures were constructed through sequence-specific peptide encoding (GYK tripeptide and Ac-IIIGYK-NH₂ hexapeptide) and co-assembly with catecholamines of graded hydrophobicity. Structural dynamics were analyzed via molecular simulations, HPLC, AFM, and spectroscopy. Hydrophobic groups (e.g., isopropyl in isoprenaline) formed compact cores that isolated chromophores from water quenching, significantly enhance fluorescence intensity and red-shifting emission by ∼40 nm. Molecular dynamics simulations confirmed hydrophobic shielding reduced water penetration, extending exciton lifetimes. Antiparallel β-sheet hexapeptides templated nanoribbons, enabling pH-switchable assembly/disassembly (stable at pH 8.0; quenched below pH 7). Tyrosinase-responsive co-assemblies induced selective cytotoxicity in B16 melanoma cells. This work establishes a supramolecular design paradigm where peptide-catecholamine interfacial interactions govern hydrophobic confinement, enabling programmable fluorescence tuning and targeted bio-applications.