Using modified aptamers for site specific protein-aptamer conjugationsElectronic supplementary information (ESI) available: All experimental details are written as a separate section in the SI materials. These include the synthetic procedures, testing protocols etc. They are written in detail and are complete. See DOI: 10.1039/c5sc02631h

Conjugation of DNA to defined locations on a protein surface will be a powerful tool for positioning functional groups and molecules in biological and biomedical studies. However, tagging protein with DNA is challenging in physiological environments, and requires a bioorthogonal approach. Here, we report a chemical solution to selectively conjugate DNA aptamers with a protein by protein-aptamer template (PAT)-directed reactions. Since protein-aptamer interactions are bioorthogonal, we exploit the PAT as a unique platform for specific DNA-protein cross-linking. We develop a series of modified oligonucleotides for PAT-directed reactions and find an F-carboxyl group as a suitable functionality for selective and site-specific conjugation. The functionality is incorporated into aptamers in our F-carboxyl phosphoramidite with an easy synthesis. We also demonstrate the necessity of a linker between the reactive functionality and the aptamer sequences. We have developed a new method for the selective conjugation of target proteins at lysine residues through a protein-aptamer template-directed reaction.