title: Bipyridyl- and biphenyl-DNA: a recognition motif based on interstrand aromatic stacking.
abstract: The synthesis and incorporation into oligonucleotides of C-nucleosides containing the two aromatic, non-hydrogen-bonding nucleobase substitutes biphenyl (I) and bipyridyl (Y) are described. Their homo- and hetero-recognition properties in different sequential arrangements were then investigated via UV-melting curve analysis, gel mobility assays, CD- and NMR spectroscopy. An NMR analysis of a dodecamer duplex containing one biphenyl pair in the center, as well as CD data on duplexes with multiple insertions provide further evidence for the zipper-like interstrand stacking motif that we proposed earlier based on molecular modeling. UV-thermal melting experiments with duplexes containing one to up to seven I- or Y base pairs revealed a constant increase in T(m) in the case of I and a constant decrease for Y. Mixed I/Y base pairs lead to stabilities in between the homoseries. Insertion of alternating I/abasic site- or Y/abasic site pairs strongly decreases the thermal stability of duplexes. Asymmetric distribution of I- or Y residues on either strand of the duplex were also investigated in this context. Duplexes with three natural base pairs at both ends and 50 % of I pairs in the center are still readily formed, while duplexes with blunt ended I pairs tend to aggregate unspecifically. Duplexes with one natural overhang at the end of a I-I base pair tract can both aggregate or form ordered duplexes, depending on the nature of the natural bases in the overhang.
authors.affiliation: Department of Chemistry and Biochemistry, University of Bern, Freiestrasse 3, 3012 Bern, Switzerland.
authors.forename: Christine
authors.initials: C
authors.lastname: Brotschi
authors.forename: Gérald
authors.initials: G
authors.lastname: Mathis
authors.forename: Christian J
authors.initials: CJ
authors.lastname: Leumann
mesh_terms: D015082:2,2'-Dipyridyl / Q000031:analogs & derivatives / Q000737:chemistry*; D001713:Biphenyl Compounds / Q000737:chemistry*; D002942:Circular Dichroism; D004247:DNA / Q000138:chemical synthesis / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D015394:Molecular Structure; D009841:Oligonucleotides / Q000138:chemical synthesis* / Q000737:chemistry; D012680:Sensitivity and Specificity
chemical_list: D001713:Biphenyl Compounds; D009841:Oligonucleotides; D015082:2,2'-Dipyridyl; D004247:DNA