Rational and combinatorial design of peptide capping ligands for gold nanoparticles.

Based on protein folding considerations, a pentapeptide ligand, CALNN, which converts citrate-stabilized gold nanoparticles into extremely stable, water-soluble gold nanoparticles with some chemical properties analogous to those of proteins, has been designed. These peptide-capped gold nanoparticles can be freeze-dried and stored as powders that can be subsequently redissolved to yield stable aqueous dispersions. Filtration, size-exclusion chromatography, ion-exchange chromatography, electrophoresis, and centrifugation can be applied to these particles. The effect of 58 different peptide sequences on the electrolyte-induced aggregation of the nanoparticles was studied. The stabilities conferred by these peptide ligands depended on their length, hydrophobicity, and charge and in some cases resulted in further improved stability compared with CALNN, yielding detailed design criteria for peptide capping ligands. A simple strategy for the introduction of recognition groups is proposed and demonstrated with biotin and Strep-tag II.