Interchain cross-linking of DNA mediated by the principal adduct of acrolein.
A DNA duplex containing the primary acrolein adduct, 3-(2-deoxy-beta-D-erythro-pentofuranosyl)-5,6,7,8-tetrahydro-8-hydroxypyrimido[1,2-a]purin-10(3H)-one (2), of deoxyguanosine in a 5'-CpG sequence context spontaneously but reversibly formed an interchain cross-link with the exocyclic amino group of deoxyguanosine in the opposing chain. The linkage was sufficiently stable that the cross-linked duplex could be isolated by HPLC and characterized by MALDI-TOF mass spectrometry. Enzymatic degradation gave bis-nucleoside 6, which was independently prepared by direct reaction of 2 with dGuo.
Kozekov
I D
ID
Department of Chemistry and Center in Molecular Toxicology, Vanderbilt University, Nashville, TN 37235, USA.
Nechev
L V
LV
Sanchez
A
A
Harris
C M
CM
Lloyd
R S
RS
Harris
T M
TM
D000171:Acrolein / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D003432:Cross-Linking Reagents; D018736:DNA Adducts / Q000737:chemistry*; D003849:Deoxyguanosine / Q000737:chemistry; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D003432:Cross-Linking Reagents; D018736:DNA Adducts; D000171:Acrolein; D003849:Deoxyguanosine