Crystal structures of DNA duplexes stabilized by bicyclic-C residues.
Chemical modification of nucleic acids is being studied extensively as an approach for the development of nucleic acid-based therapies. We found that a nucleotide carrying 7,8-dihydropyrido[2,3-d]pyrimidin-2-one (bicyclic-C or X), which is a cytosine derivative with a propene attached at the N4 and C5 atoms, increases the stability of DNA duplexes. To establish the conformational effects of X on DNA and to obtain insight 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 2.9 A resolutions. In both duplexes, the bicyclic-C bases form pairs with the counter bases through hydrogen bonds, and stabilize the duplex formation in part by stacking interactions between X and the subsequent thymine base of the same strand.
Haraguchi
Tsuyoshi
T
Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Yokohama 226-8501, Japan.
Shimizu
Satoru
S
Ma
Xiao
X
Kurose
Taizo
T
Juan
Ella Czarina Magat
EC
Ohkubo
Akihiro
A
Sekine
Mitsuo
M
Shibata
Takayuki
T
Millington
Christopher L
CL
Williams
David M
DM
Takénaka
Akio
A
D020137:Base Pair Mismatch; D018360:Crystallography, X-Ray; D003596:Cytosine / Q000031:analogs & derivatives* / Q000737:chemistry; D004247:DNA / Q000737:chemistry*; D008958:Models, Molecular; D009690:Nucleic Acid Conformation
C520055:7,8-dihydropyrido(2,3-d)pyrimidin-2-one; D003596:Cytosine; D004247:DNA