Solution-phase bioconjugate synthesis using protected oligonucleotides containing 3'-alkyl carboxylic acids

Protected oligonucleotides containing 3'-alkyl carboxylic acids are obtained from a photolabile solid-phase synthesis support (lb). The protected oligonucleotides are efficiently conjugated (>80%) with amines in solution to yield products of high purity under mild reaction conditions. This method is particularly well-suited for the synthesis of oligonucleotide-peptide conjugates containing a covalent linkage between the 3' terminus of an oligonucleotide and the amino terminus of a peptide. High yields of nucleopeptides are obtained even when the peptide contains a hindered N- terminal amino acid.