Biochemistry of Actinomycins.

The toxicity and biological activity of actinomycins at all levels of biological organi zation investigated to date are based on their ability to form tight, reversible complexes with DNA. The presence of guanine in a DNA preparation, preferably in the helical configuration, is necessary and sufficient for the formation of the characteristic complexes. Bound actinomycin produces alterations in the physical properties of DNA including increased viscosity, failure to assume the A configuration under appropriate conditions, and marked increases in “meltingtemperature. These changes have their counter pant in the morphological distortions seen in isolated preparations on in salivary gland cells of Drosophila. At the enzymatic and cellular level DNA-directed RNA synthesis is very sensitive to actinomycin, whereas the replication of DNA itself is relatively resistant. The for mation of all species of RNA is blocked by actinomycin in all uninfected, susceptible organisms, but the growth of most RNA viruses is unaffected by the antibiotic. The use of actinomycin has permitted some investigation of the physiology of tem plate RNA, the functioning of which has shown considerable stability in a number of systems. The biological activity of actinomycin is abolished by changes involving any of the major structural features of the molecule.