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Actinomycin binding to DNA: Mechanism and specificity

1965; Elsevier BV; Volume: 11; Issue: 3 Linguagem: Inglês

10.1016/s0022-2836(65)80001-8

1089-8638

Martin Gellert, C. E. Smith, David M. Neville, Gary Felsenfeld,

Metal complexes synthesis and properties

The interaction, of actinomycin with DNA is found to involve two classes of sites. Measurements are reported here of the properties of the strongly binding sites, which appear to be the ones involved in the biological activity of actinomycin as an inhibitor of DNA-dependent RNA synthesis. It is found that the binding of actinomycin to dGMP involves a favorable enthalpy change and a decrease in entropy, whereas the binding to the DNA sites which are studied here involves a large increase in entropy and no enthalpy change. The probable source of the entropy increase is the disruption of actinomycin-solvent interaction; the entropy of solution of actinomycin is shown to be large and negative at room temperature. Measurements of the effect of disruption of helical structure upon actinomycin binding demonstrate that this structure is essential to the binding. Titration experiments with a series of DNA's reveal the dependence of the number of strongly binding sites in the helical structure upon base composition. The dependence can be accounted for either by a site which consists of a sequence of two base pairs, involving one G-C pair and one A-T pair, or by a site consisting entirely of G-C pairs, in which there is a large amount of steric interference between sites spaced more closely than five to six base pairs apart.