RESUMEN
A convergent strategy was employed to link eight 10-27-mer peptides to oligonucleotide phosphorothioates, resulting in twenty-six various conjugates. A stepwise synthesis strategy for the preparation of peptide-oligonucleotide phosphorothioate conjugates, employing Fmoc peptide chemistry, was developed and applied to the synthesis of four conjugates. Three of these conjugates contained either a 10 or 16-mer peptide, incorporating either 2 or 3 arginine residues, respectively.
Asunto(s)
Oligonucleótidos/síntesis química , Péptidos/síntesis química , Tionucleótidos/síntesis química , Secuencia de Aminoácidos , Aminoácidos/química , Arginina/química , Química Orgánica/métodos , Fluorenos/química , Datos de Secuencia Molecular , Oligonucleótidos/química , Péptidos/química , Tionucleótidos/químicaRESUMEN
Eighteen peptide-oligonucleotide phosphorothioate conjugates were prepared in good yield and thoroughly characterized with electrospray ionization mass spectra. When applied to the living cells, conjugates exhibiting membrane translocation and nuclear localization properties displayed efficient intracellular penetration but failed to show any serious antisense effect. Studies on the intracellular distribution of the fluorescein-labeled conjugates revealed their trapping in endosomes.
