Efficient incorporation of a copper hydroxypyridone base pair in DNA.
Recently, we reported the first artificial nucleoside for alternative DNA base pairing through metal complexation (J. Org. Chem. 1999, 64, 5002-5003). In this regard, we report here the synthesis of a hydroxypyridone-bearing nucleoside and the incorporation of a neutral Cu(2+)-mediated base pair of hydroxypyridone nucleobases (H-Cu-H) in a DNA duplex. When the hydroxypyridone bases are incorporated into the middle of a 15 nucleotide duplex, the duplex displays high thermal stabilization in the presence of equimolar Cu(2+) ions in comparison with a duplex containing an A-T pair in place of the H-H pair. Monitoring temperature dependence of UV-absorption changes verified that a Cu(2+)-mediated base pair is stoichiometrically formed inside the duplex and dissociates upon thermal denaturation at elevated temperature. In addition, EPR and CD studies suggested that the radical site of a Cu(2+) center is formed within the right-handed double-strand structure of the oligonucleotide. The present strategy could be developed for controlled and periodic spacing of neutral metallobase pairs along the helix axis of DNA.
Tanaka
Kentaro
K
Department of Chemistry, Graduate School of Science, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
Tengeiji
Atsushi
A
Kato
Tatsuhisa
T
Toyama
Namiki
N
Shiro
Motoo
M
Shionoya
Mitsuhiko
M
D020029:Base Pairing; D002942:Circular Dichroism; D003300:Copper / Q000737:chemistry*; D004247:DNA / Q000138:chemical synthesis* / Q000737:chemistry; D004578:Electron Spin Resonance Spectroscopy; D009690:Nucleic Acid Conformation; D009705:Nucleosides / Q000138:chemical synthesis / Q000737:chemistry; D009711:Nucleotides / Q000138:chemical synthesis / Q000737:chemistry; D009841:Oligonucleotides / Q000138:chemical synthesis / Q000737:chemistry; D009942:Organometallic Compounds / Q000737:chemistry; D011728:Pyridones / Q000737:chemistry*; D013056:Spectrophotometry, Ultraviolet
D009705:Nucleosides; D009711:Nucleotides; D009841:Oligonucleotides; D009942:Organometallic Compounds; D011728:Pyridones; D003300:Copper; D004247:DNA