Actinomycins
Actinomycin are a class of peptide - antibiotics from Streptomyces .
Structural structure
Actinomycins are chromopeptides. As a common actinoyl chromophore, they have a 2-amino phenoxazin -3-one system, which is doubly methylated and linked to pentapeptide lactone rings via two amide bonds . Actinomycin D can be regarded as the basic structure , from which the other structures can be derived by modifying or modifying individual amino acids . In addition to the proteinogenic amino acids L- threonine , L- valine and L- proline , actinomycin D also contains the non-proteinogenic amino acids sarcosine and D- valine . Two identical peptide lactone rings are called iso- actinomycins, and different rings are called aniso -actinomycins. Over 20 different actinomycins of natural origin are known.
Discovery and Nomenclature
Actinomycin A was isolated from Streptomyces antibioticus by Selman A. Waksman in 1940 and was the first antibiotic obtained from actinomycetes . The further investigations showed that it was a mixture of several individual components. These mixtures, known as complexes, were also found in different compositions in other streptomycetes and identified with Latin letters; the individual components of a complex were named using 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
Actinomycin intercalation reversibly with double-stranded DNA , the chromophore pushes thereby selectively between two guanine / cytosine - base pairs . As a result of intercalation , replication and transcription are disturbed because the corresponding enzymes use DNA as a template. The transcription is much stronger and therefore inhibited even at lower concentrations than the replication. This preference arises from the different conformation of the DNA in the active center of DNA and RNA polymerase , which in the case of RNA polymerase causes a stronger binding of actinomycin.
Pharmacological application
Due to the non-selective mechanism of action , the cytostatic and antibacterial activity is associated with high toxicity . Nevertheless, actinomycin D is used as a chemotherapeutic agent for some types of cancer , e.g. B. in combination with vincristine for the treatment of certain kidney tumors or soft tissue sarcomas and Ewing sarcomas in children ( Wilms tumor ).
Use in cell biology
The 7-amino derivative (7-AAD) of actinomycin D is called fluorescence - dye for DNA in the fluorescence microscopy and flow cytometry used.
literature
- AB Mauger, H. Lackner: The Actinomycins. In: Anticancer Agents from Natural Products. (Eds .: DGI Kingston, GM Cragg, DJ Newman), CRC Press, Boca Raton, 2005, pp. 281-298.
- U. Keller, F. Schauwecker: Nonribosomal Biosynthesis of Chromopeptides. In: Prog. Nucleic Acid Res. Mol. Biol. 2001, 70, 233-289. PMID 11642364
- GH Jones, U. Keller: Biochemistry and Genetics of Actinomycin Production. In: Drugs and the Pharmaceutical Sciences. 1997, 82, 335-361.
- AB Mauger: The Actinomycins. In: Topics in Antibiotic Chemistry. 1980, 5, 229-306.
- H. Lackner: The spatial structure of the actinomycins. In: Angew. Chem. 1975, 87, 400-411. doi : 10.1002 / anie.19750871104
Individual evidence
- ↑ Gill, JE et al. (1975): 7-Amino-actinomycin D as a cytochemical probe. I. Spectral properties. In: J. Histochem. Cytochem. Vol. 23, pp. 793-799, PMID 1194669 PDF ( Memento of September 27, 2007 in the Internet Archive ).