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首页> 外文期刊>The Journal of Antibiotics: An International Journal >Possible structural role of the disaccharide unit in Fe-bleomycin before and after oxygen activation
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Possible structural role of the disaccharide unit in Fe-bleomycin before and after oxygen activation

机译:氧激活前后铁博来霉素中二糖单元的可能结构作用

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Our previous investigation of the solution structure of Fe(II)-bleomycin pointed toward the carbamoyl group in the mannose moiety or a water molecule as possible alternative axial ligands to the metal center in this metallo-bleomycin. The possibility of a solvent molecule occupying the apical position trans to the primary amine has not been ruled out yet. In order to explore this possibility even further, the coordination chemistry of azide-bound Fe(II)-bleomycin was investigated with the use of NMR applied to paramagnetic molecules. Fe(II)- and apo-bleomycin were also re-visited. Comparison of the NMR results for both Fe(II)-bound molecules obtained in the present study strongly suggests that the carbamoyl oxygen is ligated to Fe(II), and it is released from coordination upon azide binding. This event is suggested based on the diminished paramagnetic character exhibited by the carbohydrate moiety in Fe(II)-azide-bleomycin when compared with its parent metal complex. A possible structural role for the glucopyranose fragment, which changes throughout the process that starts with metallo-bleomycin formation and ends with DNA binding, is discussed. The study of the coordination of azide by Fe(II)-bleomycin through NMR has not been reported previously. Unlike magnetic CD data, NMR offers a residue-by-residue account of the possible structural changes that take place in Fe(II)-bleomycin after azide binding.
机译:我们之前对Fe(II)-博来霉素溶液结构的研究指出,甘露糖部分中的氨基甲酰基或水分子可能是该金属博来霉素中金属中心可能的替代轴向配体。尚未排除溶剂分子占据顶位至伯胺的可能性。为了进一步探讨这种可能性,利用应用于顺磁性分子的NMR研究了叠氮化物结合的Fe(II)-博来霉素的配位化学。 Fe(II)-和载脂霉素也被重新检查。比较在本研究中获得的两个与Fe(II)结合的分子的NMR结果,强烈表明氨基甲酰氧与Fe(II)连接,并在叠氮化物结合后从配位体中释放出来。该事件是根据Fe(II)-叠氮化物-博来霉素中的碳水化合物部分与其母体金属配合物相比所表现出的顺磁特性减弱而提出的。讨论了吡喃葡萄糖片段的可能的结构作用,该过程在整个过程中都会发生变化,该过程从金属博来霉素的形成开始到以DNA结合结束。以前尚未报道过Fe(II)-博来霉素通过NMR对叠氮化物的配位研究。与磁性CD数据不同,NMR提供了一个叠氮残基,说明叠氮化物结合后Fe(II)-博来霉素中可能发生的结构变化。

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