Synthesis of DNA conjugates by solid-phase fragment condensation via aldehyde–nucleophile coupling

Abstract

Oligodeoxyribonucleotides were synthesized that contain a novel nucleoside, 2′- O-(2,3-dihydroxypropyl)cytidine. Its 2′-diol group was blocked by an allyloxycarbonyl protecting group. Selective deprotection of diol group(s) of the support-immobilized blocked oligodeoxyribonucleotide by Pd(0) followed by periodate oxidation resulted in generation of the 2′-aldehyde group(s) on solid-phase. The modified oligonucleotides were used to prepare a number of conjugates with acridine, biotin and N-modified laminin peptides by oxime, hydrazone and hydrazine formation. The method may be applicable to the synthesis of oligonucleotide–peptide conjugates.