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Arar, K ; Aubertin, AM ; Roche, AC ; Monsigny, M ; Mayer, R

Synthesis and antiviral activity of peptide-oligonucleotide conjugates prepared by using n-a-(bromoacetyl)peptides

Bioconjugate Chemistry 6 (5) 573-577

par Administrateur - publié le

Abstract :

Antisense oligonucleotides represent an interesting tool for selective inhibition of gene expression. In order to direct oligonucleotides to specific compartments within the cell, we have investigated the possibility of coupling them to a signal peptide Lys-Asp-Glu-Leu (KDEL). This sequence should be able to convey oligonucleotides to the endoplasmic reticulum and from there to the cytosol and the nucleus where their targets are located. On this basis we prepared peptide-oligonucleotide conjugates by coupling, in a single step, a N-a-bromoacetyl peptide with an oligonucleotide bearing a thiol group, through a thioether bond. This paper deals with the definition of the optimal pH and temperature conditions leading to an efficient synthesis of peptide-oligonucleotide conjugates : the reaction was quantitative at pH 7.5 within few hours.