EFFECT OF THE TERMINAL PHOSPHATE DERIVATIZATION OF BETA-OLIGODEOXYNUCLEOTIDES AND ALPHA-OLIGODEOXYNUCLEOTIDES ON THEIR ANTISENSE ACTIVITY IN PROTEIN-BIOSYNTHESIS, STABILITY AND UPTAKE BY EUKARYOTIC CELLS

被引：26

作者：

BOUTORINE, AS ^{[1
]}

BOIZIAU, C ^{[1
]}

LEDOAN, T ^{[1
]}

TOULME, JJ ^{[1
]}

HELENE, C ^{[1
]}

机构：

[1] MUSEUM NATL HIST NAT,BIOPHYS LAB,F-75231 PARIS 05,FRANCE

来源：

BIOCHIMIE | 1992年 / 74卷 / 05期

关键词：

ANTISENSE ALPHA-OLIGONUCLEOTIDE; ALKYLATING DERIVATIVE; TRANSLATION INHIBITION; CHEMICAL MODIFICATION; HYDROPHOBIC DERIVATIVE; CELLULAR UPTAKE;

D O I：

10.1016/0300-9084(92)90089-W

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：

Inhibition of polypeptide chain elongation with the mRNA-complementary (antisense) oligonucleotide has been realized through a RNase H independent mechanism. Nuclease resistant complementary non-natural alpha-17-mer oligonucleotide did not inhibit cell-free protein biosynthesis of beta-globin in the wheat germ system because it did not elicit RNase H activity. Linkage of alkylating group [4-(N-2-chloroethyl-N-methyl)-aminobenzyl]-methylamine to the 5'-terminus of the alpha-oligomer led to the formation of its covalent adduct with mRNA which could not be translated in vitro. Linkage of hydrophobic residues to the terminal phosphates of natural oligonucleotides increased their stability against nucleases and uptake by human cancer cells. A porphyrin, substituted in the meso-position by aromatic groups, gave a rise to an approximately six-fold increase of uptake and cholesterol a 30-100-fold increase. Eighty percent of bound derivatives were found in cytoplasmic cellular fractions.

引用

页码：485 / 489

页数：5

共 13 条

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