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Dynamic Combinatorial Nanoparticles for Protein Surface Recognition

Final Report Summary - DCN (Dynamic Combinatorial Nanoparticles for Protein Surface Recognition)

We prepared gold nanoparticles (AuNPs) decorated with functional groups as the platform of dynamic combinatorial chemistry (DCC) for biomacromolecule recognition purpose. For bio-compatibility reason, hydrazone chemistry was employed in water at physiological pH in the presence of aniline as catalyst. AuNPs were pre-coated with aldehyde groups, and then further multi-functionalised in dynamic combinatorial libraries (DCLs) by reacting with a pool of hydrazides carrying potential binding sites.

To obtain water-soluble gold nanoparticles functionalised with aldehyde, different aldehyde ligands and water-solubilising ligands were synthesised. AuNPs with aldehyde groups were successfully prepared with these ligands by different methods. The size of AuNPs was determined to be proper for biomacromolecule recognition (< 15 nm). The formation and exchange of the hydrazones were confirmed with various characterisation methods by adding hydrazides one after another, and no aggregation or obvious morphology change was observed during this process. After the reversible hydrazone chemistry reached the thermodynamic equilibrium, the hydrazides were cleaved from the surface of AuNPs through hydrazone / oxime exchange and product distribution was analysed.

The recognition of biomacromolecules were carried out by exposing the DCL to short sequence double stranded DNAs. The equilibrium of DCL was significantly shifted and cationic hydrazide, which showed strong interaction with polyphosphate backbones of DNA, was amplified by 14 times. Some other bio-interesting molecules such as nucleoside phosphates also showed template effect on the DCLs.