The crystal and molecular structure of the anticancer drug actinomycin D—some explanations for its unusual properties

Abstract

Abstract The crystal structure of the antitumor antibiotic actinomycin D has been determined by the methods of x‐ray crystallography. There are three independent molecules in the asymmetric unit. Two of the molecules form a hydrogen‐bonded dimer. The peptides within all three molecules have very similar conformations. The greatest conformational variability in the drug molecules occurs in the torsion angles of the bonds connecting the phenoxazone ring to the peptide rings. The results of this analysis has allowed us to explain the unusual physical properties of ActD as well as to provide an explanation for the thermodynamics of its interactions with DNA.