Sequence-Selective Cleavage of Oligoribonucleotides by 3d Transition Metal Complexes of 1,5,9-Triazacyclododecane-Functionalized 2'-O-Methyl Oligoribonucleotides
详细信息 查看全文
- 作者：Teija Niittymä ; ki and Harri Lö ; nnberg
- 刊名：Bioconjugate Chemistry
- 出版年：2004
- 出版时间：November 2004
- 年：2004
- 卷：15
- 期：6
- 页码：1275 - 1280
- 全文大小：109K
- 年卷期：v.15,no.6(November 2004)
- ISSN：1520-4812
文摘
2'-O-Methyl oligoribonucleotides bearing a 3'-[2,6-dioxo-3,7-diaza-10-(1,5,9-triazacyclododec-3-yl)decylphospate conjugate group have been shown to cleave in slight excess of Zn2+ ions complementaryoligoribonucleotides at the 5'-side of the last base-paired nucleotide. The cleavage obeys first-orderkinetics and exhibits turnover. The acceleration compared to the monomeric Zn2+ 1,5,9-triazacyclododecane chelate is more than 100-fold. In addition, 2'-O-methyl oligoribonucleotides having the1,5,9-triazacyclododec-3-yl group tethered to the anomeric carbon of an intrachain 2-deoxy-
-D-erythro-pentofuranosyl group via a 2-oxo-3-azahexyl, 2,6-dioxo-3,7-diazadecyl, or 2,9-dioxo-3,10-diazatridecyllinker have been studied as cleaving agents. These cleave as zinc chelates a tri- and pentaadenylbulge opposite to the conjugate group approximately 50 times as fast as the monomeric chelate andshow turnover. The cleavage rate is rather insensitive to the length of linker. Interestingly, a triuridylbulge remains virtually intact in striking contrast to a triadenyl bulge. Evidently binding of the zincchelate to a uracil base prevents its catalytic action. Replacement of Zn2+ with Cu2+ or Ni2+ retardsthe cleaving activity of all the cleaving agents tested.
-D-erythro-pentofuranosyl group via a 2-oxo-3-azahexyl, 2,6-dioxo-3,7-diazadecyl, or 2,9-dioxo-3,10-diazatridecyllinker have been studied as cleaving agents. These cleave as zinc chelates a tri- and pentaadenylbulge opposite to the conjugate group approximately 50 times as fast as the monomeric chelate andshow turnover. The cleavage rate is rather insensitive to the length of linker. Interestingly, a triuridylbulge remains virtually intact in striking contrast to a triadenyl bulge. Evidently binding of the zincchelate to a uracil base prevents its catalytic action. Replacement of Zn2+ with Cu2+ or Ni2+ retardsthe cleaving activity of all the cleaving agents tested.