title: Toward high yield synthesis of peptide-oligonucleotide chimera through a disulfide bridge: a simplified method for oligonucleotide activation.
abstract: During the last decade, cell penetrating peptides (CPP) have been extensively used to mediate the cellular delivery of non-permeant biomolecules, including oligonucleotides (ONs). A covalent linkage between the CPP and the transported ON is required to mediate efficient cell internalization, and a disulfide bridge between the CPP and the ON has been shown to induce the most potent biological response. In this paper, we describe the activation. In a one step process of the sulfhydryl function from a synthon commercially available for ON synthesis. In addition, since the highly cationic nature of currently used CPP caused serious precipitation problems during the coupling step, we further improved the method by adsorbing the crude activated ON on an anion exchange matrix prior to specific peptide coupling.
authors.affiliation: UMR 5124 , CNRS-Université Montpellier II, 5 Place Eugène Bataillon, 34095 Montpellier cedex 5, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Maurel
authors.forename: Françoise
authors.initials: F
authors.lastname: Debart
authors.forename: Florine
authors.initials: F
authors.lastname: Cavelier
authors.forename: Alain R
authors.initials: AR
authors.lastname: Thierry
authors.forename: Bernard
authors.initials: B
authors.lastname: Lebleu
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Vasseur
authors.forename: Eric
authors.initials: E
authors.lastname: Vivès
mesh_terms: D002851:Chromatography, High Pressure Liquid; D004220:Disulfides / Q000737:chemistry*; D015394:Molecular Structure; D009841:Oligonucleotides / Q000138:chemical synthesis* / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D004220:Disulfides; D009841:Oligonucleotides; D010455:Peptides