Nucleoproteins, in which the hydroxy group of a serine, a threonine, or a tyrosine, is linked through a phosphodiester group to the 3'-or 5'-end of DNA or RNA, play decisive roles in important biological processes. They may even have a major part in the process of viral replication by nucleoprotein-primed elongation of the oligonucleotide strand. For the study of the biological phenomena, in which nucleoproteins are involved, nucleopeptides with the characteristic linkage between the peptide chain and the oligonucleotide of their parent nucleoproteins may serve as powerful tools. However, the synthesis of these compounds is complicated by their pronounced acid-and base-lability, as well as their multifunctionality. As a result, protecting groups, which can be removed under the mildest conditions, are required. For the construction of such peptide conjugates using a flexible building block strategy, a combination of enzyme-labile and chemical protecting groups was developed. The C-terminal blocking function can be removed selectively from fully protected nucleoamino acid methyl, 2-methoxyethyl (ME), and methoxyethoxyethyl (MEE) esters by saponification of the esters. After elongation of the peptide chain with amino acid or peptide methyl, ME, MEE, and choline esters, the C-terminal ester blocking group can again be removed easily. The methyl, ME, and MEE esters are cleaved off with lipase, and the choline ester group is selectively attacked by butyrylcholine esterase. The nucleoamino acids and peptides formed may be fully deprotected. To this end, the enzyme-labile N-phenylacetyl (PhAc) group, which was employed to mask the amino functions of the nucleobases, was removed. The O-acetate in the deoxyribose was saponified, and the allyl protecting groups present were cleaved by Pd 0 -mediated allyl transfer. By combination of these techniques, a nucleopeptide was produced, which represents the characteristic linkage region of the nucleoprotein of adenovions 2. The conditions, under which the enzymatic deprotections proceed, are so mild that no undesired side reaction is observed, that is no depurination or b elimination of the nucleosides occurs. In addition, the specificity of the biocatalysts ensures that the peptide bonds and the other protecting groups present are not attacked either.