title: Synthesis and characterization of oligonucleotides containing a nitrogen mustard formamidopyrimidine monoadduct of deoxyguanosine.
abstract: N(5)-Substituted formamidopyrimidine adducts have been observed from the reaction of dGuo or DNA with aziridine containing electrophiles, including nitrogen mustards. However, the role of substituted Fapy-dGuo adducts in the biological response to nitrogen mustards and related species has not been extensively explored. We have developed chemistry for the site-specific synthesis of oligonucleotides containing an N(5)-nitrogen mustard Fapy-dGuo using the phosphoramidite approach. The lesion was found to be a good substrate for Escherichia coli endonuclease IV and formamidopyrimidine glycosylase.
authors.affiliation: Departments of Chemistry and Biochemistry, Center in Molecular Toxicology, and Vanderbilt-Ingram Cancer Center, Vanderbilt University , Nashville, Tennessee 37235, United States.
authors.forename: Plamen P
authors.initials: PP
authors.lastname: Christov
authors.forename: Kyu-Jun
authors.initials: KJ
authors.lastname: Son
authors.forename: Carmelo J
authors.initials: CJ
authors.lastname: Rizzo
mesh_terms: D001483:Base Sequence; D018736:DNA Adducts / Q000737:chemistry; D004260:DNA Repair; D043382:DNA-Formamidopyrimidine Glycosylase / Q000378:metabolism; D003849:Deoxyguanosine / Q000737:chemistry*; D043223:Deoxyribonuclease IV (Phage T4-Induced) / Q000378:metabolism; D004587:Electrophoresis, Agar Gel; D004926:Escherichia coli / Q000201:enzymology; D029968:Escherichia coli Proteins / Q000378:metabolism; D007700:Kinetics; D008466:Mechlorethamine / Q000737:chemistry*; D009841:Oligonucleotides / Q000138:chemical synthesis* / Q000737:chemistry; D009943:Organophosphorus Compounds / Q000138:chemical synthesis / Q000737:chemistry; D011743:Pyrimidines / Q000737:chemistry*
chemical_list: D018736:DNA Adducts; D029968:Escherichia coli Proteins; D009841:Oligonucleotides; D009943:Organophosphorus Compounds; D011743:Pyrimidines; C434331:phosphoramidite; D008466:Mechlorethamine; C039544:4,6-diamino-5-N-formamidopyrimidine; D043223:Deoxyribonuclease IV (Phage T4-Induced); C468972:endonuclease IV, E coli; D043382:DNA-Formamidopyrimidine Glycosylase; D003849:Deoxyguanosine