Actinomycins with altered threonine units in the β-peptidolactone
Actinomycins with altered threonine units in the β-peptidolactone
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DOI：
10.1021/np060063g
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发表时间：
2006-08-25
影响因子：
5.1
通讯作者：
Zeeck, Axel
中科院分区：
文献类型：
--
作者：
Bitzer, Jens;Gesheva, Victoria;Zeeck, Axel
放线菌素G（2）-G（6）（2-6）是放线菌素家族的五个新成员，由链霉菌DSM 41873菌株产生。它们的结构经波谱方法确证。与放线菌素D（1）不同，新化合物的R-环含有不常见的氨基酸3-羟基-5-甲基脯氨酸，而β-环包括N-甲基丙氨酸和氯化或羟基化苏氨酸部分。主要产物为含氯放线菌素G（2）（2），具有较强的细胞毒和抗菌活性。放线菌素G（5）（5）是第一个在β-肽内酯和放线酰发色团之间具有额外闭环的放线菌素。放线菌素G（6）（6）是由含4-羟基苏氨酸的放线菌素G（3）（3）通过β-单元的2倍酰基转移而产生的，这在这类色肽中以前没有观察到。化合物5和6的结构修饰沿着生物活性的明显降低。并对异放线菌素的生物合成进行了讨论。
Five new members of the actinomycin family, actinomycins G(2)-G(6) (2-6), are produced by Streptomyces iakyrus strain DSM 41873. Their structures were established by spectroscopic methods. Unlike actinomycin D (1), the R-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 G(2) (2) is the main product; it exhibits strong cytotoxic and antibacterial activities. Actinomycin G(5) (5) is the first actinomycin with an additional ring closure between the beta-peptidolactone and the actinoyl chromophore. Actinomycin G(6) (6) resulted from the 4-hydroxythreonine-containing actinomycin G(3) (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.