Solution structure of a DNA duplex containing a biphenyl pair.
Hydrogen-bonding and stacking interactions between nucleobases are considered to be the major noncovalent interactions that stabilize the DNA and RNA double helices. In recent work we found that one or multiple biphenyl pairs, devoid of any potential for hydrogen bond formation, can be introduced into a DNA double helix without loss of duplex stability. We hypothesized that interstrand stacking interactions of the biphenyl residues maintain duplex stability. Here we present an NMR structure of the decamer duplex d(GTGACXGCAG) d(CTGCYGTCAC) that contains one such X/Y biaryl pair. X represents a 3'',5''-dinitrobiphenyl- and Y a 3'',4''-dimethoxybiphenyl C-nucleoside unit. The experimentally determined solution structure shows a B-DNA duplex with a slight kink at the site of modification. The biphenyl groups are intercalated side by side as a pair between the natural base pairs and are stacked head to tail in van der Waals contact with each other. The first phenyl rings of the biphenyl units each show tight intrastrand stacking to their natural base neighbors on the 3'-side, thus strongly favoring one of two possible interstrand intercalation structures. In order to accommodate the biphenyl units in the duplex the helical pitch is widened while the helical twist at the site of modification is reduced. Interestingly, the biphenyl rings are not static in the duplex but are in dynamic motion even at 294 K.
Laboratory of Organic Chemistry, ETH Zürich, Wolfgang-Pauli-Strasse 10, 8093 Zürich, Switzerland.
Zeena
Z
Johar
Alain
A
Zahn
Christian J
CJ
Leumann
Bernhard
B
Jaun
D020029:Base Pairing; D001483:Base Sequence; D001713:Biphenyl Compounds / Q000737:chemistry*; D003198:Computer Simulation; D004247:DNA / Q000737:chemistry* / Q000235:genetics; D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions; D009682:Magnetic Resonance Spectroscopy; D009691:Nucleic Acid Denaturation; D009705:Nucleosides / Q000737:chemistry; D012996:Solutions; D013816:Thermodynamics; D044366:Transition Temperature
D001713:Biphenyl Compounds; D004247:DNA; D009705:Nucleosides; D012996:Solutions; C010574:biphenyl