2DPB

Crystal Structure of d(CGCGAATXCGCG) Where X is 5-(N-aminohexyl)carbamoyl-2'-deoxyuridine

Summary for 2DPB

• Entry DOI: 10.2210/pdb2dpb/pdb
• Related: 2DP7 2DPC
• Descriptor: DNA (5'-D(*DCP*DGP*DCP*DGP*DAP*DAP*DTP*DUP*DCP*DGP*DCP*DG)-3'), (6-AMINOHEXYL)CARBAMIC ACID, POTASSIUM ION, ... (4 entities in total)
• Functional Keywords: modified nucleotide, 5-(n-aminohexyl)carbamoyl-2'-deoxyuridine, b-dna, dna
• Total number of polymer chains: 2
• Total formula weight: 7658.26

Authors

Juan, E.C.M.,Kondo, J.,Kurihara, T.,Ito, T.,Ueno, Y.,Matsuda, A.,Takenaka, A. (deposition date: 2006-05-08, release date: 2007-04-17, Last modification date: 2023-10-25)

Primary citation

Juan, E.C.M.,Kondo, J.,Kurihara, T.,Ito, T.,Ueno, Y.,Matsuda, A.,Takenaka, A.
Crystal structures of DNA:DNA and DNA:RNA duplexes containing 5-(N-aminohexyl)carbamoyl-modified uracils reveal the basis for properties as antigene and antisense molecules
Nucleic Acids Res., 35:1969-1977, 2007

PubMed Abstract: Oligonucleotides containing 5-(N-aminohexyl)carbamoyl-modified uracils have promising features for applications as antigene and antisense therapies. Relative to unmodified DNA, oligonucleotides containing 5-(N-aminohexyl)carbamoyl-2'-deoxyuridine ((N)U) or 5-(N-aminohexyl)carbamoyl-2'-O-methyluridine ((N)U(m)), respectively exhibit increased binding affinity for DNA and RNA, and enhanced nuclease resistance. To understand the structural implications of (N)U and (N)U(m) substitutions, we have determined the X-ray crystal structures of DNA:DNA duplexes containing either (N)U or (N)U(m) and of DNA:RNA hybrid duplexes containing (N)U(m). The aminohexyl chains are fixed in the major groove through hydrogen bonds between the carbamoyl amino groups and the uracil O4 atoms. The terminal ammonium cations on these chains could interact with the phosphate oxygen anions of the residues in the target strands. These interactions partly account for the increased target binding affinity and nuclease resistance. In contrast to (N)U, (N)U(m) decreases DNA binding affinity. This could be explained by the drastic changes in sugar puckering and in the minor groove widths and hydration structures seen in the (N)U(m) containing DNA:DNA duplex structure. The conformation of (N)U(m), however, is compatible with the preferred conformation in DNA:RNA hybrid duplexes. Furthermore, the ability of (N)U(m) to render the duplexes with altered minor grooves may increase nuclease resistance and elicit RNase H activity.

PubMed: 17341465
DOI: 10.1093/nar/gkl821

Experimental method

X-RAY DIFFRACTION (1.5 Å)