Chemical Methods for Peptide-Oligonucleotide Conjugate Synthesis

Methods of peptide-oligonucleotide conjugate synthesis are presented that may be useful in the study of cell targeting and delivery of oligonucleotides and their analogs. The first method involves total stepwise solid-phase synthesis on a single support. The second involves preparation of oligonucleotides containing 2′-aldehydes and subsequent chemoselective ligation with functionalized peptides to form hydrazine, oxime, or thiazolidine linkages.