Abstract
THE remarkable inhibitory effect of actinomycin D on DNA dependent RNA synthesis has been correlated with its ability to interact in a specific way with the DNA template1. The nature of the sites of interaction has been investigated by physicochemical and biochemica1 methods2–4. For this purpose several chemical modifications of the actinomycin have been tried. Studies of simple chemical analogues of actinomycin which lack the peptide lactone moiety have, however, probably been discouraged by the great decrease in water solubility which is produced by the removal of the non-phenoxazone region of the molecule. Previous experiments in our laboratory have provided useful information on the interaction between DNA and polycyclic aromatic hydrocarbons5,6, which are sparingly soluble in water, through the introduction of a technique based on solubilization phenomena. This method has been used in the present work in order to study the interaction of DNA with two model compounds containing the chromophore group of actinomycin: These compounds were prepared from 2-methoxy-toluic acid (Aldrich) through either five or six steps, respectively7–9. Their solubilities in DNA solutions and in water were determined according to the technique described earlier5,6. Fine crystals of AMD 1 and AMD 2 were equilibrated with solutions of DNA (Sigma, type 1) or with doubly distilled water for 3 days at 25° C by gentle shaking in the dark.
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