The toxicity and biological activity of actinomycins at all levels of biological organization 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 “melting temperature. These changes have their counterpart in the morphological distortions seen in isolated preparations or 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 formation 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 template 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.

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Abbreviations used in this paper:

  1. A, T, U, G, C—adenine, thymine, uracil, guanine, and cytosine, respectively.

  2. poly A, poly U, poly G, poly C—3′ → 5′, polymeric ribonucleoside monophosphates of adenine, uracil, guanine, and cytosine, respectively.

  3. ATP, UTP, GTP, CTP—ribonucleoside 5′ triphosphates of adenine, uracil, guanine, and cytosine, respectively.

  4. NTP—ribonucleoside-5′-triphosphate.

  5. RNA—ribonucleic acid.

  6. DNA—deoxyribonucleic acid.

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