Actinomycins with altered threonine units in the beta-peptidolactone.
Five new members of the actinomycin family, actinomycins G2-G6 (2-6), are produced by Streptomyces iakyrus strain DSM 41873. Their structures were established by spectroscopic methods. Unlike actinomycin D (1), the alpha-ring of the novel compounds contains the unusual amino acid 3-hydroxy-5-methylproline, while the beta-ring includes N-methylalanine and either a chlorinated or hydroxylated threonine moiety. The chlorine-containing actinomycin G2 (2) is the main product; it exhibits strong cytotoxic and antibacterial activities. Actinomycin G5 (5) is the first actinomycin with an additional ring closure between the beta-peptidolactone and the actinoyl chromophore. Actinomycin G6 (6) resulted from the 4-hydroxythreonine-containing actinomycin G3 (3) by a 2-fold acyl shift of the beta-unit, which has not been observed before for this class of chromopeptides. The structural modification of compounds 5 and 6 goes along with an evident reduction of the biological activity. The biosynthesis of aniso-actinomycins is discussed.
Bitzer
Jens
J
Institute of Organic and Biomolecular Chemistry, University of Göttingen, Tammannstrasse 2, D-37077 Göttingen, Germany.
Gesheva
Victoria
V
Zeeck
Axel
A
D001412:Bacillus subtilis / Q000187:drug effects; D002176:Candida albicans / Q000187:drug effects; D032084:Citrus sinensis / Q000737:chemistry; D003609:Dactinomycin / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D004926:Escherichia coli / Q000187:drug effects; D006801:Humans; D007557:Israel; D007783:Lactones / Q000737:chemistry; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D013211:Staphylococcus aureus / Q000187:drug effects; D013237:Stereoisomerism; D013302:Streptomyces / Q000737:chemistry*; D013329:Structure-Activity Relationship; D013912:Threonine / Q000737:chemistry*; D014407:Tumor Cells, Cultured
D007783:Lactones; D003609:Dactinomycin; D013912:Threonine