title: Concise postsynthetic preparation of oligonucleotide-oligopeptide conjugates through facile disulfide bond formation.
abstract: BACKGROUND
  Despite recent advances, major hurdles still need to be cleared for widespread application of therapeutic antisense technologies. In particular, pharmacokinetic properties and efficient cellular uptake need to be improved through chemical derivatization or bioconjugation.
  
  
  RESULTS
  The 2'-O-thioethylene nucleotide building block affords easy implementation into standard oligonucleotide synthesis protocols and was used to attach oligolysine chains to phosphodiester oligonucleotides by direct reaction with S-sulfonate protected peptides. Efficient gene silencing was induced in a cell culture model after transfection reagent-free application of the conjugates.
  
  
  CONCLUSIONS
  A facile optimized procedure for generating oligonucleotide-peptide conjugates was established. The attachment of short basic peptides via a labile linker is sufficient to enhance membrane permeability of oligonucleotides and result in successful gene silencing.
authors.affiliation: Department of Pharmaceutical Chemistry, University of Vienna, Althanstraße 14, 1090 Vienna, Austria.
authors.forename: Mehrdad
authors.initials: M
authors.lastname: Dirin
authors.affiliation: Department of Pharmaceutical Chemistry, University of Vienna, Althanstraße 14, 1090 Vienna, Austria.
authors.forename: Ernst
authors.initials: E
authors.lastname: Urban
authors.affiliation: Department of Pharmaceutical Chemistry, University of Vienna, Althanstraße 14, 1090 Vienna, Austria.
authors.forename: Bodo
authors.initials: B
authors.lastname: Lachmann
authors.affiliation: Department of Pharmaceutical Chemistry, University of Vienna, Althanstraße 14, 1090 Vienna, Austria.
authors.forename: Christian R
authors.initials: CR
authors.lastname: Noe
authors.affiliation: Department of Pharmaceutical Chemistry, University of Vienna, Althanstraße 14, 1090 Vienna, Austria.
authors.forename: Johannes
authors.initials: J
authors.lastname: Winkler
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000493:pharmacokinetics* / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D004220:Disulfides / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000494:pharmacology; D020868:Gene Silencing / Q000187:drug effects; D006801:Humans; D008239:Lysine / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000494:pharmacology; D008545:Melanoma / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D009841:Oligonucleotides / Q000138:chemical synthesis* / Q000493:pharmacokinetics* / Q000494:pharmacology; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000493:pharmacokinetics* / Q000494:pharmacology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics
chemical_list: D000970:Antineoplastic Agents; D004220:Disulfides; D009841:Oligonucleotides; D009842:Oligopeptides; D019253:Proto-Oncogene Proteins c-bcl-2; D008239:Lysine