title: Synthesis of C-5, C-2' and C-4'-neomycin-conjugated triplex forming oligonucleotides and their affinity to DNA-duplexes.
abstract: Neomycin-conjugated homopyrimidine oligo 2'-deoxyribonucleotides have been synthesized on a solid phase and their potential as triplex forming oligonucleotides (TFOs) with DNA-duplexes has been studied. For the synthesis of the conjugates, C-5, C-2' and C-4'-tethered alkyne-modified nucleoside derivatives were used as an integral part of the standard automated oligonucleotide chain elongation. An azide-derived neomycin was then conjugated to the incorporated terminal alkynes by Cu(I)-catalyzed 1,3-dipolar cycloaddition (the click chemistry). Concentrated ammonia released the desired conjugates in acceptable purity and yields. The site of conjugation was expectedly important for the Hoogsteen-face recognition: C-5-conjugation showed a notable positive effect, whereas the influence of the C-2' and C-4'-modification remained marginal. In addition to conventional characterization methods (UV- and CD-spectroscopy), (19)F NMR spectroscopy was applied for the monitoring of triplex/duplex/single strand-conversions.
authors.affiliation: Department of Chemistry, University of Turku, 20014 Turku, Finland.
authors.forename: Ville
authors.initials: V
authors.lastname: Tähtinen
authors.affiliation: Department of Chemistry, University of Turku, 20014 Turku, Finland.
authors.forename: Lotta
authors.initials: L
authors.lastname: Granqvist
authors.affiliation: Department of Chemistry, University of Turku, 20014 Turku, Finland. Electronic address: pamavi@utu.fi.
authors.forename: Pasi
authors.initials: P
authors.lastname: Virta
mesh_terms: D000480:Alkynes / Q000737:chemistry; D001386:Azides / Q000737:chemistry; D002384:Catalysis; D002942:Circular Dichroism; D057930:Click Chemistry; D003300:Copper / Q000737:chemistry; D061565:Cycloaddition Reaction; D004247:DNA / Q000737:chemistry* / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D009682:Magnetic Resonance Spectroscopy; D009355:Neomycin / Q000737:chemistry*; D009690:Nucleic Acid Conformation; D009841:Oligonucleotides / Q000138:chemical synthesis / Q000737:chemistry*; D044366:Transition Temperature; D014466:Ultraviolet Rays
chemical_list: D000480:Alkynes; D001386:Azides; D009841:Oligonucleotides; D003300:Copper; D004247:DNA; D009355:Neomycin
keywords: (19)F NMR spectroscopy; Aminoglycosides; Oligonucleotide conjugates; Triple helices; Triplex forming oligonucleotides