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含膦酸甲酯核苷酸间连接和2'-O-甲基核糖核苷的寡核苷酸类似物的相互作用。

Interactions of oligonucleotide analogs containing methylphosphonate internucleotide linkages and 2'-O-methylribonucleosides.

作者信息

Kean J M, Cushman C D, Kang H, Leonard T E, Miller P S

机构信息

Department of Biochemistry, School of Hygiene and Public Health, Johns Hopkins University, Baltimore, MD 21205.

出版信息

Nucleic Acids Res. 1994 Oct 25;22(21):4497-503. doi: 10.1093/nar/22.21.4497.

DOI:10.1093/nar/22.21.4497
PMID:7526343
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC308485/
Abstract

The interactions of oligonucleotide analogs, 12-mers, which contain deoxyribo- or 2'-O-methylribose sugars and methylphosphonate internucleotide linkages with complementary 12-mer DNA and RNA targets and the effect of chirality of the methylphosphonate linkage on oligomer-target interactions was studied. Oligomers containing a single Rp or Sp methylphosphonate linkage (type 1) or oligomers containing a single phosphodiester linkage at the 5'-end followed by 10 contiguous methylphosphonate linkages of random chirality (type 2) were prepared. The deoxyribo- and 2'-O-methylribo- type 1 12-mers formed stable duplexes with both the RNA and DNA as determined by UV melting experiments. The melting temperatures, Tms, of the 2'-O-methylribo-12-mer/RNA duplexes (49-53 degrees C) were higher than those of the deoxyribo-12mer/RNA duplexes (31-36 degrees C). The Tms of the duplexes formed by the Rp isomers of these oligomers were approximately 3-5 degrees C higher than those formed by the corresponding Sp isomers. The deoxyribo type 2 12-mer formed a stable duplex, Tm 34 degrees C, with the DNA target and a much less stable duplex with the RNA target, Tm < 5 degrees C. In contrast, the 2'-O-methylribo type 2 12-mer formed a stable duplex with the RNA target, Tm 20 degrees C, and a duplex of lower stability with the DNA target, Tm < 5 degrees C. These results show that the previously observed greater stability of oligo-2'-O-methylribonucleotide/RNA duplexes versus oligodeoxyribonucleotide/RNA duplexes extends to oligomers containing methylphosphonate linkages and that the configuration of the methylphosphonate linkage strongly influences the stability of the duplexes.

摘要

研究了含有脱氧核糖或2'-O-甲基核糖糖以及甲基膦酸酯核苷酸间连接键的12聚体寡核苷酸类似物与互补的12聚体DNA和RNA靶标的相互作用，以及甲基膦酸酯连接键的手性对寡聚物-靶标相互作用的影响。制备了含有单个Rp或Sp甲基膦酸酯连接键的寡聚物（1型）或在5'-端含有单个磷酸二酯连接键，随后是10个连续的随机手性甲基膦酸酯连接键的寡聚物（2型）。通过紫外熔解实验确定，脱氧核糖型和2'-O-甲基核糖型1型12聚体与RNA和DNA均形成了稳定的双链体。2'-O-甲基核糖-12聚体/RNA双链体的熔解温度（Tm）（49-53℃）高于脱氧核糖-12聚体/RNA双链体的熔解温度（31-36℃）。这些寡聚物的Rp异构体形成的双链体的Tm比相应的Sp异构体形成的双链体的Tm高约3-5℃。脱氧核糖型2型12聚体与DNA靶标形成了稳定的双链体，Tm为34℃，与RNA靶标形成的双链体稳定性则低得多，Tm<5℃。相反，2'-O-甲基核糖型2型12聚体与RNA靶标形成了稳定的双链体，Tm为20℃，与DNA靶标形成的双链体稳定性较低，Tm<5℃。这些结果表明，先前观察到的寡聚2'-O-甲基核糖核苷酸/RNA双链体相对于寡脱氧核糖核苷酸/RNA双链体具有更高的稳定性，这一现象延伸至含有甲基膦酸酯连接键的寡聚物，并且甲基膦酸酯连接键的构型强烈影响双链体的稳定性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e27/308485/35fad578c957/nar00045-0153-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e27/308485/35fad578c957/nar00045-0153-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e27/308485/35fad578c957/nar00045-0153-a.jpg

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