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

Protected oligonucleotides containing 3'-alkyl carboxylic acids are obtaine d from a photolabile solid-phase synthesis support (1b). The protected olig onucleotides are efficiently conjugated (>80%) with amines in solution to y ield products of high purity under mild reaction conditions. This method is particularly well-suited for the synthesis of oligonucleotide-peptide conj ugates containing a covalent linkage between the 3' terminus of an oligonuc leotide and the amino terminus of a peptide. High yields of nucleopeptides are obtained even when the peptide contains a hindered N-terminal amino aci d.