Total stepwise solid-phase synthesis of oligonucleotide-(3′→N)-peptide conjugates

An efficient total stepwise solid-phase synthesis of oligonucleotide-(3'-->N)-peptide conjugates is described that makes use of either a controlled pore glass support or macroporous polystyrene beads. Extending our previous homoserine linker approach, we prepared a range of conjugates containing one of four different cell or nuclear penetration peptides together with oligonucleotides containing 2'-deoxynucleoside or 2'-O-methylribonucleoside phosphodiesters, or gapmers containing 2'- deoxyphosphorothioates. The route also allows incorporation of a fluorescent label within the conjugate for cell uptake studies.