INTERACTIONS OF OLIGONUCLEOTIDE ANALOGS CONTAINING METHYLPHOSPHONATE INTERNUCLEOTIDE LINKAGES AND 2'-O-METHYLRIBONUCLEOSIDES

被引：20

作者：

KEAN, JM ^{[1
]}

CUSHMAN, CD ^{[1
]}

KANG, HM ^{[1
]}

LEONARD, TE ^{[1
]}

MILLER, PS ^{[1
]}

机构：

[1] JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT BIOCHEM,BALTIMORE,MD 21205

来源：

NUCLEIC ACIDS RESEARCH | 1994年 / 22卷 / 21期

关键词：

D O I：

10.1093/nar/22.21.4497

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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-12-mer/ 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-methyl ribonucleotide/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.

引用

页码：4497 / 4503

页数：7

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