Nucleosides, nucleotides and oligonucleotides containing enzymatically cleavable protecting groups

摘要

Process for the production of oligonucleotides of formula II, in which the exocyclic amino groups of the bases adenine, guanine, cytosine, 7-deazaadenine and 7-deazaguanine carry N-phenylacetyl groups, are used for oligonucleotide synthesis, wherein in a first step a starting nucleotide is bound to a solid carrier, subsequently the desired oligonucleotide is synthesized by stepwise coupling with appropriately activated further monomeric nucleotide building blocks of the general formula I with the above-mentioned meanings, if desired, trivalent phosphorus is oxidized to pentavalent phosphorus during and after the synthesis, the oligonucleotide is cleaved from the carrier and the 5' protecting groups are cleaved off. The phenylacetyl functional groups that protect exocyclic NH2 groups of the bases can be cleaved off in a mild way with penicillin amidohydrolase (EC 3.5.1.11).