Use of nucleosides and nucleoside derivatives with enzymatically cleavable protecting groupes in the synthesis of oligonucleotiden

摘要

Process for the preparation of oligonucleotides of the 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 bonded to a solid support, subsequently the required oligonucleotide is assembled by stepwise coupling with appropriately activated further monomeric nucleotide building blocks of the general formula I with the abovementioned meanings, where appropriate trivalent phosphorus is oxidised to pentavalent phosphorus during and after the synthesis, the oligonucleotide is eliminated from the support and the 5'-protective groups are eliminated. The phenylacetyl groups which protect exocyclic NH2 groups on the bases can be eliminated in mild manner using penicillin amidohydrolase (EC 3.5.1.11).