Self-assembly of bivalent protein-binding agents based on oligonucleotide-linked organic fragments

A library of bidentate fragments linked through an oligonucleotide duplex was tested for binding to streptavidin. When one fragment was biotin, only biotin-containing duplexes were selected by streptavidin but when heated above the melting temperature, only bidentate biotin ligands were obtained. Thermal denaturation experiments showed that the melting temperature, thus stability, of the monodentate versus bidentate binding ligand increased from 59 to 71 °C in the presence of streptavidin. Substituting biotin with 2-iminobiotin led to the exclusion of all other duplexes by the bidentate iminobiotin duplex in binding streptavidin.

A library of bidentate fragments linked through an oligonucleotide duplex was tested for protein binding. Thermal denaturation experiments showed that the melting temperature, thus stability, of the bidentate binding ligand increased from 59 to 71 °C in the presence of protein.Figure optionsDownload as PowerPoint slide