Di(azacrown) Conjugates of 2'-O-Methyl Oligoribonucleotides as Sequence-Selective Artificial Ribonucleases

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• 作者：Teija Niittym&auml ; ki ; Pasi Virta ; Kaisa Ketom&auml ; ki ; Harri Lö ; nnberg
• 刊名：Bioconjugate Chemistry
• 出版年：2007
• 出版时间：September 2007
• 年：2007
• 卷：18
• 期：5
• 页码：1583 - 1592
• 全文大小：230K
• 年卷期：v.18,no.5(September 2007)
• ISSN：1520-4812

文摘

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)--D-ribofuranoside,and 2-hydroxyethyl 2'-O-(2-hydroxyethyl)--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)--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.