title: Conjugation of peptides to antisense interleukin-6 via click chemistry.
abstract: Low molecular weight oligonucleotides have been discovered to have potential use for gene therapy by selectively inhibiting the expression of certain genes. Chemical conjugation of functional peptides to oligonucleotides can introduce desired properties to the oligonucleotides, such as cell-specific delivery, cellular uptake efficiency, and/or intracellular distribution. In this paper, targeting peptides are conjugated to antisense interleukin-6 via a copper (I) catalyzed alkyne-azide cycloaddition click reaction. A simple and reproducible solution-phase conjugation procedure was investigated. Oligonucleotide-peptide conjugations were characterized by reverse-phase high-pressure liquid chromatography and mass spectrometry. The results show that the targeting peptides can be used for targeting delivery of oligonucleotides using the aforementioned conjugation.
authors.forename: Chang-Fang
authors.initials: CF
authors.lastname: Wang
authors.forename: Seppo
authors.initials: S
authors.lastname: Auriola
authors.forename: Jouni
authors.initials: J
authors.lastname: Hirvonen
authors.affiliation: Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, FI-00014 University of Helsinki, Helsinki, Finland. chang-fang.wang@helsinki.fi.
authors.forename: Hélder A
authors.initials: HA
authors.lastname: Santos
mesh_terms: D000480:Alkynes / Q000737:chemistry; D001386:Azides / Q000737:chemistry; D057930:Click Chemistry; D003300:Copper / Q000737:chemistry; D061565:Cycloaddition Reaction; D006801:Humans; D015850:Interleukin-6 / Q000737:chemistry*; D015394:Molecular Structure; D058990:Molecular Targeted Therapy; D016376:Oligonucleotides, Antisense / Q000138:chemical synthesis / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry*
chemical_list: D000480:Alkynes; D001386:Azides; C508600:IL6 protein, human; D015850:Interleukin-6; D016376:Oligonucleotides, Antisense; D010455:Peptides; D003300:Copper