| Abstract
| - Aminoglycoside conjugates of 2′-O-methyl oligoribonucleotides have been synthesized entirely on a solid phase using conventional phosphoramidate chemistry. For this purpose, appropriately protected neamine-derived phosphoramidites, viz., 2-cyanoethyl [6,3′,4′-tri-O-levulinoyl-N1,N3,N2′,N6′-tetra(trifluoroacetyl)neamine-5-O-ethyl] N,N-diisopropylphosphoramidite, 1, and 2-cyanoethyl [6,3′,4′,2″,3″-penta-O-levulinoyl-N1,N3,N2′,N6′-tetra(trifluoroacetyl) ribostamycin-5″-yl] N,N-diisopropylphosphoramidite, 2, have been prepared and attached via phosphodiester linkage to an appropriate 2′-O-methyl oligoribonucleotide. Levulinoyl esters are used to cap the hydroxyl groups of the aminoglycoside moieties, since they may be selectively removed prior to ammonolysis. In this manner, the potential O→N acyl migration is excluded. Applicability of the strategy has been demonstrated by the synthesis of eight different aminoglycoside conjugates, in which 1 and 2 are attached directly to the 5′-end (6 and 10) or, alternatively, to an inserted non-nucleosidic hydroxyalkyl armed branching unit (3, 4, or 5), which results in intrachain conjugates (7-9, 11-13). The potential of these conjugates to act as a sequence-selective artificial nuclease has been studied.
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