TRIPLE-HELIX FORMATION BY ALPHA OLIGODEOXYNUCLEOTIDES AND ALPHA OLIGODEOXYNUCLEOTIDE INTERCALATOR CONJUGATES

被引：109

作者：

SUN, JS ^{[1
]}

GIOVANNANGELI, C ^{[1
]}

FRANCOIS, JC ^{[1
]}

KURFURST, R ^{[1
]}

MONTENAYGARESTIER, T ^{[1
]}

ASSELINE, U ^{[1
]}

SAISONBEHMOARAS, T ^{[1
]}

THUONG, NT ^{[1
]}

HELENE, C ^{[1
]}

机构：

[1] CNRS, CTR BIOPHYS MOLEC, F-45071 ORLEANS, FRANCE

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 1991年 / 88卷 / 14期

关键词：

HUMAN IMMUNODEFICIENCY VIRUS;

D O I：

10.1073/pnas.88.14.6023

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Base-pair sequences in double-stranded DNA can be recognized by homopyrimidine oligonucleotides that bind to the major groove at homopurine-homopyrimidine sequences thereby forming a local triple helix. To make oligodeoxynucleotides resistant to nucleases, we replaced the natural (beta) anomers of the nucleotide units by the synthetic (alpha) anomers. The 11-mer-alpha-oligodeoxynucleotide 5'-d(TCTCCTCCTTT)3' binds to the major groove of DNA in an antiparallel orientation with respect to the homopurine strand, whereas a beta-oligonucleotide adopts a parallel orientation. When an intercalating agent was attached to the 3' end of the alpha-oligodeoxynucleotide, a strong stabilization of the triple helix was observed. A 16-base-pair homopurine-homopyrimidine sequence of human immunodeficiency virus proviral DNA was chosen as a target for a 16-mer homopyrimidine alpha-oligodeoxynucleotide. A restriction enzyme that cleaves DNA at the junction of the homopurine-homopyrimidine sequence was inhibited by triple-helix formation. The 16-mer-alpha-oligodeoxynucleotide substituted by an intercalating agent was almost-equal-to 20 times more efficient than the unsubstituted oligomer. Nuclease-resistant alpha-oligodeoxynucleotides offer additional possibilities to control gene expression at the DNA level.

引用

页码：6023 / 6027

页数：5

共 32 条

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