An extended phosphate linkage: Synthesis, hybridization and modeling studies of modified oligonucleotides

被引：11

作者：

Haly, B ^{[1
]}

Bellon, L ^{[1
]}

Mohan, V ^{[1
]}

Sanghvi, Y ^{[1
]}

机构：

[1] ISIS PHARMACEUT,DEPT MED CHEM,CARLSBAD,CA 92008

来源：

NUCLEOSIDES & NUCLEOTIDES | 1996年 / 15卷 / 7-8期

关键词：

D O I：

10.1080/07328319608002438

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：

Novel stretched oligonucleotides (A-D) containing a 3'-alpha-C-methylene phosphodiester bridge (5-atoms long) have been synthesized on an automated synthesizer utilizing phosphoramidite chemistry. The key building-block 1-[3 ''-O-beta-cyanoethyldiisopropylaminophosphiryl-2,3 -dideoxy-5-O-dimethoxytriphenylmethyl-3-C-(hydroxymethyl)-beta-D-erythro-pentofuranosyl]thymine (21) was prepared in a stereoselective manner from thymidine. Hybridization studies indicated a drop (1.8-3.0 degrees C/mod.) in affinity for the complementary RNA and DNA targets. Molecular modeling results indicated that the 5-atom modified backbone had a different geometry around the phosphodiester linkage compared to the natural phosphodiester linkage. The stretched backbone may not be useful for antisense or tripler constructs, however it may find applications in biochemical/enzyme studies.

引用

页码：1383 / 1395

页数：13

共 44 条

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