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Kuznetsova S. A., Sumbatyan N. V., Malvy C., Bertrand J. -R., Harel-Bellan A., Korshunova G. A., Svinarchuk F. P.
Synthesis of
Oligonucleotide– Peptide Conjugates: The Use of N-Hydroxybenzotriazole Esters
Abstract
Conjugates
of oligodeoxynucleotides with peptides that are potential inhibitors and
activators of gene expression were synthesized. The easy and effective method
including a condensation of 3’- or 5’-N-hydroxybenzotriazole ester of an
oligonucleotide phosphate with terminal amino group of peptide was used for
preparing covalent conjugates of two
types. The conjugates of the first type were constructed of the antisense
oligonucleotide, 5’-GAACACGCCATGTCGp-3’, complementary to the env AUG codon
region of the Friend murine leukemia virus mRNA, and the following peptides:
[Leu5]-enkephaline, [DAla2, Ual5]-enkephaline and
nucleopeptides on the base of d-ornithine,
in which a-amino
function has been modified with pyrimidyl-1- and purinyl-9-acetic acids or pyrimidyl-1- and purinyl-9-alanines. The
second type conjugates have contained two or three minimal transcriptional
activation domains derived from protein VP16, H-GGG(PADALDDFDLDML)n-OH (n=2 and 3), linked to the 3’- or 5’-end of the oligonucleotide,
5’-GGAGGAGGAGGAGGGGGAGG-3’, forming
stable triplexes with a promoter region of the HIV-2 virus vpx gene.
Copyright (C) Chemistry Dept., Moscow State University, 2002
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