Synthesis of oligonucleotides containing the N2-deoxyguanosine adduct of the dietary carcinogen 2-amino-3-methylimidazo[4,5-f]quinoline.
2-amino-3-methylimidazo[4,5-f]quinoline (IQ) is a highly mutagenic heterocyclic amine formed in all cooked meats. IQ has been found to be a potent inducer of frameshift mutations in bacteria and carcinogenic in laboratory animals. Upon metabolic activation, IQ forms covalent adducts at the C8- and N2-positions of deoxyguanosine with a relative ratio of up to approximately 4:1. We have previously incorporated the major dGuo-C8-IQ adduct into oligonucleotides through the corresponding phosphoramidite reagent. We report here the sequence-specific synthesis of oligonucleotides containing the minor dGuo-N2-IQ adduct. Thermal melting analysis revealed that the dGuo-N2-IQ adduct significantly destabilizes duplex DNA.
Stover
James S
JS
Department of Chemistry and Center in Molecular Toxicology, Vanderbilt University, Nashville, TN 37235-1822, USA.
Rizzo
Carmelo J
CJ
D002273:Carcinogens / Q000737:chemistry*; D002942:Circular Dichroism; D003849:Deoxyguanosine / Q000737:chemistry*; D019075:Electrophoresis, Capillary; D009841:Oligonucleotides / Q000138:chemical synthesis*; D009943:Organophosphorus Compounds / Q000138:chemical synthesis; D011804:Quinolines / Q000737:chemistry*
D002273:Carcinogens; D009841:Oligonucleotides; D009943:Organophosphorus Compounds; D011804:Quinolines; C434331:phosphoramidite; C029216:2-amino-3-methylimidazo(4,5-f)quinoline; D003849:Deoxyguanosine