The conjugation of macromolecules offers a rapid and versatile route to improved function. Here, the methods for obtaining disulfide-linked oligonucleotide-peptide and oligonucleotide-protein conjugates are described. These hybrid molecules can be used deliver chemical functionality to specific sequences within deoxyribonucleic acid and ribonucleic acid. The peptides and proteins can also be used to enhance the hybridization properties of the attached oligonucleotides.