Abstract:
: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.
journal_name
Biochimiejournal_title
Biochimieauthors
Boutorine AS,Boiziau C,Le Doan T,Toulmé JJ,Hélène Cdoi
10.1016/0300-9084(92)90089-wkeywords:
subject
Has Abstractpub_date
1992-05-01 00:00:00pages
485-9issue
5eissn
0300-9084issn
1638-6183pii
0300-9084(92)90089-Wjournal_volume
74pub_type
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