通过顺式和反式-4-甲基脯氨酸的生物合成掺入形成的新型放线菌素。
Novel actinomycins formed by biosynthetic incorporation of cis- and trans-4-methylproline.
作者信息
Katz E, Williams W K, Mason K T, Mauger A B
出版信息
Antimicrob Agents Chemother. 1977 Jun;11(6):1056-63. doi: 10.1128/AAC.11.6.1056.
Streptomyces parvulus (Streptomyces parvullus) normally produces actinomycin D; in the presence of cis-4-methylproline, this species synthesizes two additional actinomycins, designated K(1c) and K(2c), in which one and two proline sites, respectively, are occupied by cis-4-methylproline. Analogously, actinomycins K(1t) and K(2t) are formed in the presence of trans-4-methylproline. Both mixtures were separated chromatographically, and the four novel actinomycins were obtained in crystalline form. Their biological activities were compared with that of actinomycin D in respect to inhibition of ribonucleic acid, deoxyribonucleic acid, and protein synthesis and antimicrobial potency. In all cases examined, the order of activity D > K(1t) > K(1c) > K(2t) > K(2c) was observed, and the same sequence prevailed in a spectroscopic measure of their binding to deoxyribonucleic acid. In addition, proton nuclear magnetic resonance studies revealed that the replacement of proline by cis-4-methylproline alters the conformation of the antibiotic molecule.
小链霉菌（Streptomyces parvullus）通常产生放线菌素D；在顺式-4-甲基脯氨酸存在的情况下，该菌种会合成另外两种放线菌素，分别命名为K(1c)和K(2c)，其中分别有一个和两个脯氨酸位点被顺式-4-甲基脯氨酸占据。类似地，在反式-4-甲基脯氨酸存在的情况下会形成放线菌素K(1t)和K(2t)。两种混合物通过色谱法进行分离，得到了四种新型放线菌素的晶体形式。就对核糖核酸、脱氧核糖核酸和蛋白质合成的抑制作用以及抗菌效力而言，将它们的生物活性与放线菌素D的生物活性进行了比较。在所有检测的情况下，均观察到活性顺序为D > K(1t) > K(1c) > K(2t) > K(2c)，并且在它们与脱氧核糖核酸结合的光谱测量中也呈现相同的顺序。此外，质子核磁共振研究表明，脯氨酸被顺式-4-甲基脯氨酸取代会改变抗生素分子的构象。
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