Studies on the biological activities of actinomycins Z1 and Z5 |
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Authors: | K Mason E Katz A B Mauger |
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Institution: | Department of Microbiology, Georgetown University Schools of Medicine and Dentistry, Washington, D. C. 20007 USA;Research Foundation of the Washington Hospital Center, Washington, D. C. 20010 USA |
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Abstract: | The biological activities of actinomycins Z1, Z5, and IV (D) were compared. No consistent pattern was observed between the in vitro and in vivo results. Inhibition of E. coli DNA-dependent RNA polymerase in vitro followed the sequence IV > Z1 > Z5; however, for inhibition of RNA synthesis in B. subtilis and in HeLa cells the sequence was IV > Z5 > Z1 and the latter relationship was seen in the antimicrobial activity also. Physicochemical data did not agree with any of these findings. Difference spectra obtained with B. subtilis and M. lysodeikticus DNA followed the sequence Z1 > IV > Z5, while the relative thermal denaturation profiles were the exact opposite, Z5 > IV > Z1. These physicochemical criteria appear to be less reliable quantitative guides to biological activity. The relative ineffectiveness of actinomycin Z1in vivo is probably the result of permeability differences associated with the presence of an hydroxylated proline residue (3-hydroxy-4-oxo-5-methylproline). |
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