| Abstract
| - Functionalized 2‘-O-methyl oligoribonucleotides bearing two 3-(3-hydroxypropyl)-1,5,9-triazacyclododecane ligandsattached via a phosphodiester linkage to a single non-nucleosidic building block have been prepared on a solid-support by conventional phosphoramidite chemistry. The branching units employed for the purpose include 2,2-bis(3-hydroxypropylaminocarbonyl)propane-1,3-diol, 2-hydroxyethyl 3‘-O-(2-hydroxyethyl)-β-d-ribofuranoside,and 2-hydroxyethyl 2‘-O-(2-hydroxyethyl)-β-d-ribofuranoside. Each of these has been introduced as a phosphoramidite reagent either into the penultimate 3‘-terminal site or in the middle of the oligonucleotide chain. Thedinuclear Zn2+ complexes of these conjugates have been shown to exhibit enhanced catalytic activity over theirmonofunctionalized counterpart, the 3‘-terminal conjugate derived from 2-hydroxyethyl 3‘-O-(2-hydroxyethyl)-β-d-ribofuranoside being the most efficient cleaving agent. This conjugate cleaves an oligoribonucleotide targetat a single phosphodiester bond and shows turnover and 1000-fold cleaving activity compared to the free monomericZn2+ chelate of 1,5,9-triazacyclododecane.
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