Reaction of DNA with a mutagenic 3-N,N-acetoxyacetylamino-4,6-dimethyldipyrido[1,2-a:3',2'- d]imidazole (N-AcO-AGlu-P-3) related to glutamic acid pyrolysates.
3-Amino-4,6-dimethyldipyrido[1,2-a:3',2'-d]imidazole (Glu-P-3), an analog amine of the potent genotoxic Glu-P-1 isolated from a glutamic acid pyrolysate, has been chemically synthesized. Glu-P-3 was found much more mutagenic than Glu-P-1 to S. typhimurium TA 98 and TA 100 with S-9 mix. 3-N,N-acetoxyacetylamino-4,6-dimethyldipyrido[1,2-a:3',2'-d] imidazole (N-AcO-AGlu-P-3), a possible metabolite of Glu-P-3, binds covalently to the C-8 position of guanine residues in DNA. The binding induces large conformational changes of the macromolecule.
Loukakou
B
B
Hebert
E
E
Saint-Ruf
G
G
Leng
M
M
D004247:DNA; D003849:Deoxyguanosine; D004720:Endonucleases / Q000494:pharmacology; D006358:Hot Temperature; D007093:Imidazoles / Q000633:toxicity; D009153:Mutagens; D009690:Nucleic Acid Conformation; D015719:Single-Strand Specific DNA and RNA Endonucleases; D013056:Spectrophotometry, Ultraviolet
D007093:Imidazoles; D009153:Mutagens; C023785:2-amino-6-methyldipyrido(1,2-a-3',2'-d)imidazole; D004247:DNA; C043663:3-(N-acetoxy-N-acetylamino)-4,6-dimethyldipyrido(1,2-a-3',2'-d)imidazole; D004720:Endonucleases; D015719:Single-Strand Specific DNA and RNA Endonucleases; D003849:Deoxyguanosine