Dactinomycin
Actinomycins are a class of peptide antibiotics from Streptomyces.
Structural design
Actinomycins are Chromopeptide. They have as a common Actinoyl chromophore 2- amino-phenoxazin- 3-one system, that is two times methylated and linked through amide bonds with two Pentapeptidlacton rings. The basic structure of actinomycin D can be viewed, from which can be derived by changing or modifying individual amino acids, the other structures. In addition to the proteinogenic amino acids L -threonine, L -valine and L-proline are actinomycin D, the non-proteinogenic amino acids, sarcosine and D- valine. When two equal Peptidlactonringen is called iso- actinomycins in different rings of aniso - actinomycins. There are over 20 different known actinomycins natural origin.
Discovery and nomenclature
Actinomycin A was Selman A. Waksman 1940 from Streptomyces antibioticus isolated and was the first antibiotic obtained from actinomycetes. Further investigations showed that it was a mixture of several individual components. These so-called Complex mixtures were found in different combinations in other streptomycetes and marked with Roman letters, the designation of the individual components of a complex was carried out by a number as an index. Since the mixtures found often contained the same substances but in different proportions, there are a number of synonymous names for most actinomycins.
Biological effect
Actinomycins intercalate reversibly with double-stranded DNA, the chromophore pushes thereby selectively between two guanine / cytosine - base pairs. Due to the intercalation of replication and transcription to be disturbed, because the corresponding enzymes using DNA as a template. Transcription is much stronger and therefore already at lower concentrations inhibited than replication. This preference arises from the different conformation of the DNA at the active site of DNA and RNA polymerase, which causes a stronger bond of actinomycin in the case of RNA polymerase.
Pharmacological application
Due to the non-selective mode of action the cytostatic and anti-bacterial activity is associated with a high toxicity. Nevertheless, actinomycin D comes as a chemotherapeutic agent in some cancers is applied, eg in combination with vincristine for the treatment of certain renal tumors or soft tissue sarcoma and Ewing's sarcoma in children ( Wilms' tumor).
Use in cell biology
The 7-amino derivative ( 7-AAD ) of actinomycin D is used as a fluorescent dye for DNA in fluorescence microscopy and flow cytometry.