Synthesis of a Glycomimetic Oligonucleotide Conjugate by 1,3-Dipolar Cycloaddition

A glycomimetic oligonucleotide conjugate bearing four galactose residues on a mannose core is �synthesized using oligonucleotide solid-phase synthesis and Cu(I)-catalyzed azide-alkyne 1,3-dipolar cycloaddition (CuAAC, or “click” chemistry). To achieve this purpose, new building blocks (including the solid support and phosphoramidites) are synthesized and used on a DNA synthesizer to generate a tetraalkyne oligonucleotide, which is then conjugated with a galactose azide derivative by click chemistry to afford the desired 3′-tetragalactosyl-mannose oligonucleotide conjugate. The procedures described in this chapter provide a general approach for the synthesis of novel glycoconjugates that can be immobilized to a DNA chip via DNA-directed immobilization to study, for example, their multivalent interactions with lectins in cellular targeting/uptake, etc.