Stepwise Solid‐Phase Synthesis of Nucleopeptides

Phosphodiester‐linked peptide‐oligonucleotide conjugates (nucleopeptides) are obtained by stepwise solid‐phase procedures. The peptide is first assembled on a suitably derivatized solid matrix and the oligonucleotide is subsequently elongated at the free hydroxyl group of the linking amino acid. Temporary acid‐labile and permanent base‐labile protecting groups are combined. Careful choice of the protection scheme is required to prevent and minimize side reactions that may degrade the target molecule.