Synthesis and hybridization properties of oligonucleotides containing 2'-O-modified ribonucleotides.
Synthesis and hybridization properties of oligonucleotides containing 2'-O-modified ribonucleotides.
复制标题
含有 2-O-修饰核糖核苷酸的寡核苷酸的合成和杂交特性。
DOI：
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发表时间：
1993
影响因子：
14.9
通讯作者：
Robert Haner
中科院分区：
文献类型：
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作者：
Thomas H. Keller;Robert Haner
描述了一种通用的、一般的方法，用于通过在糖的2 ′-位上的简单接头将不同的官能团引入寡核苷酸中。携带亲脂性、嵌入性或叔氨基的核苷酸结构单元可以通过标准自动化寡核苷酸合成有意地放置在寡核苷酸的任何所需位置。用这些寡核苷酸进行的热变性研究揭示了以下一般趋势：i）用亲脂性正辛基基团进行的修饰对双链体稳定性几乎没有影响（如果有的话）;在寡核苷酸的末端或附近比在中间更好地耐受去稳定化（亲脂性）取代基。ii）嵌入取代基（2-氨基蒽醌）显著增加双链体稳定性。iii）N，N-二甲基氨基残基也增加双链体稳定性，尽管程度小于嵌入残基。iv）在5 '端的修饰比相应的3'端修饰对TM具有更显著的影响。v）以这种方式修饰的寡核苷酸显示出很少或没有序列特异性的损失。
A versatile, general way is described for the introduction of different functional groups into oligonucleotides by means of a simple linker at the 2'-position of the sugar. Nucleotide building blocks carrying lipophilic, intercalating or tertiary amino groups can be placed deliberately at any desired position of oligonucleotides by standard automated oligonucleotide synthesis. Thermal denaturation studies with these oligonucleotides reveal the following general trends: i) Modification with lipophilic n-octyl groups has little if any effect on duplex stability; a destabilizing (lipophilic) substituent is better tolerated at or near the ends than in the middle of the oligo. ii) An intercalating substituent (2-aminoanthraquinone) substantially increases duplex stability. iii) N,N-Dimethyl amino residues also increase duplex stability though to a smaller extent than intercalating residues. iv) Modifications at the 5'-end have a more pronounced influence on the TM than the corresponding 3'-modifications. v) Oligonucleotides modified in such a way show little or no loss in sequence specificity.