title: Synthesis and molecular modelling of double-functionalised nucleosides with aromatic moieties in the 5'-(S)-position and minor groove interactions in DNA zipper structures.
abstract: A series of six double-functionalised nucleosides, in which aromatic moieties were inserted into the 5'-(S)-C-position, were synthesised and incorporated into DNA duplexes. The aromatic moieties were thymine-1-yl, phenyl, 1,2,3-triazol-1-yl, 1,2,3-triazol-4-yl, 4-(uracil-5-yl)-1,2,3-triazol-1-yl and 4-phenyl-1,2,3-triazol-1-yl. The DNA duplexes were studied with UV melting curves, CD spectroscopy and molecular modelling. The results showed that the aromatic moieties in some cases interact in the minor groove forming DNA zipper structures. The strongest specific interaction was found between two thymines or between a thymine and a phenyl group in a crossed (-3)-zipper motif (i.e., with two base pairs interspacing the modifications). Modelling revealed that the interaction is aromatic stacking across the minor groove. Also, the extended uracil-triazole moiety demonstrated zipper contacts in the minor groove as well as binding to the floor of the groove.
authors.affiliation: Nucleic Acid Center, Department of Physics and Chemistry, University of Southern Denmark, Campusvej 55, 5230 Odense M, Denmark.
authors.forename: Khalil Isak
authors.initials: KI
authors.lastname: Shaikh
authors.forename: Charlotte Stahl
authors.initials: CS
authors.lastname: Madsen
authors.forename: Lise Junker
authors.initials: LJ
authors.lastname: Nielsen
authors.forename: Anna Søndergaard
authors.initials: AS
authors.lastname: Jørgensen
authors.forename: Henrik
authors.initials: H
authors.lastname: Nielsen
authors.forename: Michael
authors.initials: M
authors.lastname: Petersen
authors.forename: Poul
authors.initials: P
authors.lastname: Nielsen
mesh_terms: D057930:Click Chemistry; D004247:DNA / Q000737:chemistry*; D008958:Models, Molecular; D036103:Nanotechnology; D009690:Nucleic Acid Conformation; D009705:Nucleosides / Q000138:chemical synthesis* / Q000737:chemistry; D012689:Sequence Homology, Nucleic Acid
chemical_list: D009705:Nucleosides; D004247:DNA