Actinomycin composition

Naturally-occurring actinomycins show as a common feature the presence of the phenoxazinone chromophore, doubly-linked to a pentapeptide which forms a macrocyclic structure. Differences among actinomycins arise from variations in composition of the pentapeptide. The precursors of the aminoacids, forming the pentapeptide, have been singled out [176-178]. 

Certain changes in the proportion of different actinomycins synthesized by a given Streptomyces sp. may result from changes in the amino acid composition of the culture medium. Studies by Katz and Goss have indicated that addition to the medium of proline, hydrox5 roline, or sarcosine respectively may result in an increased synthesis of actinomycins with these particular residues at sites A and A, and that the addition of pipecolic acid or azetidine-2-carboxylic acid results in the production of new actinomycins in which residues of the added compounds occupy these sites. It seems that the peptide synthesizing mechanism does not distinguish perfectly, at sites A and A, between amino acids of similar structure. 

Actlnomvcin D - Kinetic studies with actinomycin D (act-D) in transplanted leukemic mice showed that a single dose provided cytotoxic concentrations for up to 24 hours,The characteristics of act-D resistance in L5178Y cells show that alterations in membrane composition and conformation in the drug-resistant subline accounts for the observed changes in the permeability of this drug.91 Act-D enhances the toxicity of morphine by increasing brain permeability. ... 

Soon after, Brockmann and Grubhofer (1949) isolated from a culture of 5. chrysomallus another actinomycin which they designated as C. It appeared to be different from actinomycin A or B on the basis of crystal form, melting point, solubihty, infrared spectrum, analytical composition and the nature of the amino acids present (Brockmann and Grubhofer, 1950,1951). Hydrolysates of actinomycin C contained the six amino acids D-valine, sarcosine, L-threonine, L-proline, N-methyl-L-valine and D-alloisoleucine. 

In addition to the actinomycins hsted above the alphabetical designations AA, AC, J, M, K and Z have been employed by other investigators to designate actinomycin preparations isolated by them (Sarlet, 1950 Sarlet, Toussaint and Brasseur, 1951 Hirata and Nakanishi, 1949 Craveri, 1956 Bossi, Hutter, Keller-Schierlein, Neipp and Zahner, 1958). Many of these are probably identical with previously described actinomycin preparations despite the use of different alphabetical appellations. The great number of actinomycins and the synonomy of many of the names have made their descriptions difficult. The various actinomycins, their synonomy and their amino acid composition are given in Table 1. 

The experimental approach in most of the systems studied so far was to follow the greening process at different levels (ultrastructure, composition of membranes, development of activity) and try to establish a correlation between the different parameters observed which will lead to the formulation of explanatory hypotheses. The validity of the hypotheses can then be assessed by inducing alteration in the process at one level and studying the effect at the other levels. The use of protein and nucleic acid synthesis inhibitors has so far been the method of choice. Cycloheximide was extensively used to block protein synthesis by cytoplasmic 80 S type ribosomes, while chloramphenicol, spectinomycin, and lyncomycin were used to inhibit protein synthesis by the chloroplast ribosomes. Actinomycin D and, more recently, rifampicin have been used as inhibitors of RNA synthesis. Initially, rifampicin was considered to be specific for the DNA-dependent RNA polymerase of the chloroplast. Although it appears that in some algae, such as Chlamydomonas and Acetabularia, rifampicin has a reasonable degree of specificity, its action against RNA polymerase of the chloroplast partially purified from plants was not found to be specific. ... 

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