Study of the Mechanism of Interaction of Oligonucleotides with the 3′-Terminal Region of tRNAPhe by Computer Modeling
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- 作者：Yu. N. Vorobjev
- 关键词：tRNA ; antisense oligonucleotides ; structure of tRNA ; oligonucleotide complexes ; computer ; based modeling
- 刊名：Molecular Biology
- 出版时间：September 2005
- 出版年：2005
- 期刊代码：44_00268933
- 类别：law
- 卷：39
- 期：5
- 页码：777-784
- 数据来源：sp
摘要
Three-dimensional atomic models of complexes between yeast tRNAPhe and 10- or 15-mer oligonucleotides complementary to the 3′-terminal tRNA sequence have been constructed using computer modeling. It has been found that rapidly formed primary complexes appear when an oligonucleotide binds to the coaxial acceptor and T stems of the tRNAPhe along the major groove, which results in the formation of a triplex. Long stems allow the formation of a sufficiently strong complex with the oligonucleotide, which delivers its 3′-terminal nucleotides to the vicinity of the T loop adjoining the stem. These nucleotides destabilize the loop structure and initiate conformational rearrangements involving local tRNAPhe destruction and formation of the final tRNAPhe-oligonucleotide complementary complex. The primary complex formation and the following tRNAPhe destruction constitute the “molecular wedge” mechanism. An effective antisence oligonucleotide should consist of three segments—(1) complex initiator, (2) primary complex stabilizer, and (3) loop destructor—and be complementary to the (free end)/loop-stem-loop tRNA structural element.