Actinomycin D (AMD) is used clinically to treat tumours such as Wilms' tumour1 and gestational choriocarcinoma2. It inhibits transcription in most cellular systems3,4, and binds to DNA, not to RNA3-5, with a preference for guanine6. The study of the crystal structure of a 2:1 complex between deoxyguanosine and AMD demonstrated both stacking and hydrogen-bonding interactions between the drug and the guanine ring7. Solution studies8,9 have indicated that the drug binds preferentially to guanine-pyrimidine sequences, such as d(GpC), and that an intercalated complex forms with both DNA10 and DNA fragments 11. External binding12 and intercalation10,13 models for the structure of the complex between AMD and DNA have been proposed, but until now no crystal strucutre of a complex between AMD and an oligonucleotide has been reported. As the smallest unit of DNA with the potential for forming an intercalated duplex is a self-complementary deoxydinucleoside monophosphate, we undertook the crystallographic analysis of the 2:1 complex between deoxyguanylyl-3′, 5′-deoxycytidine, d(GpC), and AMD. The complex is found to form an unusual pseudo-intercalated structure.
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