Nucleotide−Surface Interactions in DNA-Modified Au−Nanoparticle Conjugates: Sequence Effects on Reactivity and Hybridization

We report a systematic study of the base-dependent behavior of oligonucleotides linked to Au NP surfaces. Ten 15mer sequences were designed to investigate the effect of oligonucleotide sequence and high-affinity nucleotide location relative to the nanoparticle surface. The nucleotide position was varied within the sequence to be proximal, midway, or distal to the 5′ thiol. High-affinity motifs of adenine, guanine, and cytosine were placed in polythymine sequences, with a homobase oligonucleotide of thymine as a control sequence. Oligonucleotide reactivity toward the NPs and the extent of hybridization of the conjugates varied with sequence. Chemical treatment of the NP surface to remove nonspecific adsorption removed sequence-dependent effects on the hybridization. The behavior of the conjugates can be explained by nonspecific adsorption, where A- and C-containing oligonucleotides have a higher affinity for the NP surface.