Binding of Drugs to Supercoiled Circular DNA: Evidence for and against Intercalation

  • Michael Waring
Part of the Progress in Molecular and Subcellular Biology book series (PMSB, volume 2)

Abstract

Outstanding among molecular models for interactions between drugs and DNA is the intercalation model, originally proposed by Lerman (1961) for the binding of acridines to DNA. A primary objective of this model was to suggest a plausible molecular basis for the ability of acridine dyes, especially proflavine, to induce frame shift mutations in microorganisms. The phenomenon of frame shift mutagenesis by acridines is now firmly established (Streisinger, Okada, Emrich, Newton, Tsugita, Terzaghi and Inouye, 1966), and several suggestions have been made to account for such mutations in terms of intercalation (Brenner, Barnett, Crick and Orgel, 1961; Lerman, 1963; Streisinger et al., 1966). However, in recent years the intercalation model has become increasingly important for a different reason — namely, that it seems to account satisfactorily for the interaction between DNA and many other drugs, most of which are of interest for biological effects other than mutagenesis. These drugs include several chemotherapeutic agents, such as the trypanocide ethidium bromide (Waring, 1965, 1966), the schistosomicide Miracil D (Lucanthone) (Hirschberg, Weinstein, Gersten, Marner, Finkelstein and Carchman, 1968), the antitumour antibiotics daunomycin and nogalamycin (Ward, Reich and Goldberg, 1965; Kersten, Kersten and Szybalski, 1966), and the antimalarial drug chloroquine (O’Brien, Allison and Hahn, 1966).

Keywords

Rubber Streptomycin Ethidium Diamine Chloroquine 

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© Springer-Verlag Berlin · Heidelberg 1971

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  • Michael Waring

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