Porphyrin conjugated to DNA by a 2'-amido-2'-deoxyuridine linkage

A porphyrin that contains a single carboxylic acid group was synthesized and coupled to 2'-amino-2'-deoxyuridine. The resultant product contained a free 3' hydroxyl group and a 4,4'-dimethoxytrityl (DMT) protecting group on the 5' hydroxyl of the uridine, making it suitable for use in oligonucleotide synthesis. The 3' H-phosphonate derivative of this molecule was synthesized and used to form a conjugate with a 19 nucleotide sequence of DNA (5'-CCTCCAGTGGAAATCAAGG-3'). This was carried out with the DNA attached at the 3' end to a control pore glass (CPG) substrate, allowing for rapid purification. After removal of the DMT group, an additional three nucleotides were added, leaving the porphyrin as an internal modification. This is the first report of porphyrin attached internally to an oligonucleotide using a hydrogen-bonding nucleoside analog. This allows oligonucleotides to be used as a scaffold for precise positioning of multiple porphyrins within biomimetic arrays.