Efficient synthesis of DNA containing the guanine oxidation-nitration product 5-guanidino-4-nitroimidazole: generation by a postsynthetic substitution reaction.
[reaction: see text] A convertible nucleoside was synthesized and used to prepare the 2'-deoxynucleoside of 5-guanidino-4-nitroimidazole, a putative in vivo product of the reaction of peroxynitrite with guanine. The convertible nucleoside was incorporated into an oligodeoxynucleotide by the phosphoramidite method and converted postsynthetically to yield an oligodeoxynucleotide containing 5-guanidino-4-nitroimidazole at a specific site. The oligodeoxynucleotide was inserted into a viral genome. Melting temperature analysis revealed that duplexes containing 5-guanidino-4-nitroimidazole were greatly destabilized relative to unmodified duplexes.
Neeley
William L
WL
Department of Chemistry and Biological Engineering Division, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
Henderson
Paul T
PT
Essigmann
John M
JM
D004247:DNA / Q000138:chemical synthesis*; D003849:Deoxyguanosine / Q000138:chemical synthesis / Q000737:chemistry; D006146:Guanidines / Q000138:chemical synthesis* / Q000737:chemistry*; D006147:Guanine / Q000737:chemistry*; D015394:Molecular Structure; D009593:Nitroimidazoles / Q000138:chemical synthesis* / Q000737:chemistry*; D010084:Oxidation-Reduction
C493908:5-guanidino-4-nitroimidazole; D006146:Guanidines; D009593:Nitroimidazoles; D006147:Guanine; D004247:DNA; D003849:Deoxyguanosine