Binding specificity of mutagenic tryptophan pyrolysates for DNA conformation: spectroscopic and viscometric studies

The compounds, 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1) and 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2), are major potent mutacarcinogens isolated from tryptophan pyrolysate. In order to investigate their interaction with DNA and effects on DNA conformation, studies involving circular dichroism, fluorescence and absorption spectroscopy and viscometric titration were performed. The results show that (a) Trp-P-1 and Trp-P-2 are potent intercalators of DNA with nearly the same specificity for the A-T and G-C (alternative purine-pyrimidine) base sequences, (b) the interaction of Trp-P-1 with the B-form of DNA is biphasic so that stiffening of the B-DNA conformation occurs over the range r ([Trp-P-1]/[DNA]) = 0-2.5, followed by transformation of B to the non-B conformation at r > 2.5, (c) the transformation to the non-B structure is not observed for Trp-P-2, although stiffening of the B-DNA conformation similarly occurs, and (d) both Trp-P-1 and Trp-P-2 promote unwinding of the salt-induced Z-DNA to give the B-form. These data indicate that the noncovalent interaction of Trp-P with DNA is mainly dependent on the B-form conformation.