Interaction of mutagenic tryptophan pyrolysate with d(CGATCG)2: intercalation model based on NMR experiments

The solution structure of the complex of 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1), a potent mutacarcinogen isolated from tryptophan pyrolysate, with the hexamer duplex d(CGATCG)2, was analysed by 1H-NMR spectroscopy and molecular dynamic calculation. Trp-P-1 was intercalated between the CpG base pairings in a suitable manner to form the guanosine-Trp-P-1 adduct which corresponds to the major reactant of Trp-P-1 with DNA.