Insights into the DNA stabilizing contributions of a bicyclic cytosine analogue: crystal structures of DNA duplexes containing 7,8-dihydropyrido [2,3-d]pyrimidin-2-one.
The incorporation of the bicyclic cytosine analogue 7,8-dihydropyrido[2,3-d]pyrimidin-2-one (X) into DNA duplexes results in a significant enhancement of their stability (3-4 K per modification). To establish the effects of X on the local hydrogen-bonding and base stacking interactions and the overall DNA conformation, and to obtain insights into the correlation between the structure and stability of X-containing DNA duplexes, the crystal structures of [d(CGCGAATT-X-GCG)](2) and [d(CGCGAAT-X-CGCG)](2) have been determined at 1.9-2.9 Å resolutions. In all of the structures, the analogue X base pairs with the purine bases on the opposite strands through Watson-Crick and/or wobble type hydrogen bonds. The additional ring of the X base is stacked on the thymine bases at the 5'-side and overall exhibits greatly enhanced stacking interactions suggesting that this is a major contribution to duplex stabilization.
Magat Juan
Ella Czarina
EC
Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Yokohama 226-8501, Japan.
Shimizu
Satoru
S
Ma
Xiao
X
Kurose
Taizo
T
Haraguchi
Tsuyoshi
T
Zhang
Fang
F
Tsunoda
Masaru
M
Ohkubo
Akihiro
A
Sekine
Mitsuo
M
Shibata
Takayuki
T
Millington
Christopher L
CL
Williams
David M
DM
Takénaka
Akio
A
D020029:Base Pairing; D018360:Crystallography, X-Ray; D003596:Cytosine / Q000031:analogs & derivatives* / Q000737:chemistry; D004247:DNA / Q000737:chemistry*; D005456:Fluorescent Dyes / Q000737:chemistry; D057927:Hydrophobic and Hydrophilic Interactions; D008958:Models, Molecular; D009690:Nucleic Acid Conformation
C520055:7,8-dihydropyrido(2,3-d)pyrimidin-2-one; D005456:Fluorescent Dyes; D003596:Cytosine; D004247:DNA