Efficient methods of synthesis of peptide-oligonucleotide conjugates are badly needed for studies of uptake into cells in culture. We describe improvements to the procedures involved in "native ligation" conjugation in solution to extend the method to basic peptides. Further, we describe progress in development of a total solid-phase synthesis approach that makes use of a L-homoserine linker as the key reagent for growing of oligonucleotide and peptide chains on a single solid support.