Developing Methods for the Synthesis of Ligand–Oligonucleotide Conjugates for Drug Discovery Applications

Recently, oligonucleotide-based drug discovery has attracted considerable amounts of attention. As oligonucleotide therapeutics have evolved into practical use, research into the development of functional artificial nucleic acids has been vigorously conducted worldwide. However, the synthesis of artificial nucleic acids generally requires long sequences from starting materials; hence, structurally optimizing oligonucleotide therapeutics is extremely difficult. In response to this challenge, we have been developing reactions that use oligonucleotides as starting materials. As a part of this work, we focused on ligand-oligonucleotide conjugates because the conjugates of functional ligands and oligonucleotides have attracted attention as drug-delivery systems that improve the efficacies of oligonucleotide therapeutics; they are also DNA-encoded-library-based drug-discovery tools. In this review, we broadly introduce our research into ligand-oligonucleotide conjugates.