title: 5-Nitroindole oligonucleotides with alkynyl side chains: universal base pairing, triple bond hydration and properties of pyrene "click" adducts.
abstract: Oligonucleotides with 3-ethynyl-5-nitroindole and 3-octadiynyl-5-nitroindole 2'-deoxyribonucleosides were prepared by solid-phase synthesis. To this end, nucleoside phosphoramidites with clickable side chains were synthesized. The 3-ethynylated 5-nitroindole nucleoside was hydrated during automatized DNA synthesis to 3-acetyl-5-nitroindole 2'-deoxyribonucleoside. Side product formation was circumvented by triisopropylsilyl protection of the ethynyl side chain and was removed with TBAF after oligonucleotide synthesis. All compounds with a clickable 5-nitroindole skeleton show universal base pairing and can be functionalized with almost any azide in any position of the DNA chain. Functionalization of the side chain with 1-azidomethylpyrene afforded click adducts in which the fluorescence was quenched by the 5-nitroindole moieties. However, fluorescence was slightly recovered during duplex formation. Oligonucleotides with a pyrene residue and a long linker arm are stabilized over those with non-functionalized side chains. From the UV red shift of the pyrene residue in oligonucleotides and modelling studies, pyrene intercalation was established for the long linker adduct showing increased duplex stability over those with a short side chain.
authors.affiliation: Laboratory of Bioorganic Chemistry and Chemical Biology, Center for Nanotechnology, Heisenbergstrasse 11, 48149 Münster, Germany.
authors.forename: Sachin A
authors.initials: SA
authors.lastname: Ingale
authors.forename: Peter
authors.initials: P
authors.lastname: Leonard
authors.forename: Haozhe
authors.initials: H
authors.lastname: Yang
authors.forename: Frank
authors.initials: F
authors.lastname: Seela
mesh_terms: D020029:Base Pairing; D001483:Base Sequence; D057930:Click Chemistry; D004247:DNA / Q000138:chemical synthesis / Q000737:chemistry; D003853:Deoxyribonucleosides / Q000138:chemical synthesis / Q000737:chemistry; D007211:Indoles / Q000737:chemistry*; D008958:Models, Molecular; D009841:Oligonucleotides / Q000138:chemical synthesis* / Q000737:chemistry; D011721:Pyrenes / Q000737:chemistry*; D060327:Solid-Phase Synthesis Techniques
chemical_list: D003853:Deoxyribonucleosides; D007211:Indoles; D009841:Oligonucleotides; D011721:Pyrenes; D004247:DNA; C030984:pyrene; C090067:5-nitroindole