Synthesis of oligonucleotide conjugates via aqueous Diels-Alder cycloaddition.

The conjugation of maleimide reporter groups to 5'-diene-modified oligonucleotides via aqueous Diels-Alder cycloaddition is described. Detailed basic protocols are provided for the preparation of a diene-amidite (5'-diene modifier), for the attachment of a diene group to the 5'-terminus of oligonucleotides, and for the conjugation of maleimide reporter groups to diene-modified oligonucleotides.