title: Oligonucleotides conjugated to short lysine chains.
abstract: A new method for synthesizing oligonucleotide peptide conjugates by an in-line approach is presented. A phosphorothioate oligonucleotide with the sequence of bcl-2 targeted Oblimersen by employing a modified 2'-amino-2'-desoxy-uridine nucleotide bearing a succinyl linker at the 2' position was prepared. The carboxyl group was protected for solid-phase synthesis as the benzyl ester. Ester cleavage was afforded by a phase transfer reaction using palladium nanoparticles as catalyst and cyclohexadiene as hydrogen donor. Short tails of up to three lysyl residues were conjugated to the oligonucleotide by an inverse stepwise peptide synthesis. The conjugates were characterized by HPLC, mass spectrometry, and circular dichroism. Influence of lysyl tails on CD spectra were minimal. Melting profiles revealed only minimal destabilizing effects on duplexes by conjugation of peptides.
authors: Department of Medicinal Chemistry, Universität Wien, Althanstrasse 14, 1090 Wien, Austria.
authors: Johannes
authors: J
authors: Winkler
authors: Ernst
authors: E
authors: Urban
authors: Christian R
authors: CR
authors: Noe
mesh_terms: D002851:Chromatography, High Pressure Liquid; D002942:Circular Dichroism; D008239:Lysine / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D009841:Oligonucleotides / Q000737:chemistry*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D009841:Oligonucleotides; D008239:Lysine