Di(azacrown) conjugates of 2'-O-methyl oligoribonucleotides as sequence-selective artificial ribonucleases | doi.page

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Di(azacrown) conjugates of 2'-O-methyl oligoribonucleotides as sequence-selective artificial ribonucleases

2008pp. 378–379

Teija Niittymäki, Pasi Virta, Kaisa Ketomäki, Harri Lönnberg

Abstract

Functionalized 2‘-O-methyl oligoribonucleotides bearing two 3-(3-hydroxypropyl)-1,5,9-triazacyclododecane ligands\nattached 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,\nand 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. The\ndinuclear Zn2+ complexes of these conjugates have been shown to exhibit enhanced catalytic activity over their\nmonofunctionalized 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 target\nat a single phosphodiester bond and shows turnover and 1000-fold cleaving activity compared to the free monomeric\nZn2+ chelate of 1,5,9-triazacyclododecane.

Abstract

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