A complex of calf-thymus DNA with berberine sediments in the analytical ultracentrifuge. The DNA produced systematic changes in the absorption spectrum of berberine which suggest that single alkaloid molecules bind to DNA. Flow dichroism of purines and pyrimidines and of berberine in the complex with DNA had the same signs and magnitudes. Berberine shifted the thermal strand separation profile of DNA to higher temperatures. Therefore, the alkaloid forms a complex with DNA, probably by intercalation.

Spectrophotometric results indicated that Methyl Green bound stably to native calf thymus DNA and to poly[d(A-T)] but to a lesser extent to phiX 174 DNA, tRNAs, and poly(dG-dC), a copolymer that exists preferentially in the A conformation. Exposing the Methyl Green-DNA complex to graded concentrations of ethyl alcohol liberated part of the dye slowly by a zero-order reaction; higher alcohol concentrations which cause the B leads to A transition of DNA released the bulk of Methyl Green. The viscosity of the Methyl Green-DNA complex was significantly lower than that of the uncomplexed DNA. The dye was progressively liberated from DNA by 1.5 x 10(-1) M NaCl and by much lower concentrations of Mg2+; in its stoichiometric complex with DNA, it increased Tm by approximately 12 degrees C. A series of DNA-complexing drugs displaced Methyl Green from DNA at exponential rates and to end points which were correlated. End points of displacement correlated with the abilities of drugs to unwind supercoiled DNA, to labilize ribosomes to heat, and to eliminate a kanamycin resistance determinant from an R factor carried by Salmonella typhimurium. Additional correlations between Methyl Green displacement and biochemical-biological activities of displacing drugs are cited. In conjunction with these findings, our results suggest that Methyl Green displacement analysis is a useful biochemical screen for the detection or development of biologically active compounds which bind to DNA.

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