Lehmann T E, Ming L J, Rosen M E, Que L
Department of Chemistry, University of Minnesota, Minneapolis 55455, USA.
Biochemistry. 1997 Mar 11;36(10):2807-16. doi: 10.1021/bi962748t.
The coordination chemistry of the iron(II) complex of the antitumor drug bleomycin has been extensively investigated with a number of spectroscopic and chemical techniques. However, the actual structure of this complex is not established. In this report, we present NMR studies of the paramagnetic Fe(II)BLM and use one- and two-dimensional methods to assign the paramagnetically shifted features to particular protons. The data analysis points toward the primary and secondary amines of the beta-aminoalanine fragment, the pyrimidine and imidazole rings, and the amide nitrogen of the beta-hydroxyhistidine fragment as ligands to the metal center. Correlation of the T1 values with the metal-proton distances derived from the NMR-generated solution structure of HOO-Co(III)BLM [Wu, W., Vanderwall, D. E., Lui, S. M., Tang, X.-J., Turner, C. J., Kozarich, J. W., & Stubbe, J. (1996) J. Am. Chem. Soc. 118, 1268-1280] indicates that the two metallobleomycins share similar structures. The chemical shifts as well as the T1 values of the sugar protons indicate that these fragments are close but not bound to the metal in Fe(II)BLM.
人们已运用多种光谱和化学技术，对抗肿瘤药物博来霉素的铁（II）配合物的配位化学展开了广泛研究。然而，该配合物的实际结构尚未确定。在本报告中，我们展示了对顺磁性Fe（II）BLM的核磁共振研究，并运用一维和二维方法，将顺磁位移特征归属于特定质子。数据分析表明，β-氨基丙氨酸片段的伯胺和仲胺、嘧啶和咪唑环以及β-羟基组氨酸片段的酰胺氮是金属中心的配体。T1值与由HOO-Co（III）BLM的核磁共振生成溶液结构得出的金属-质子距离之间的相关性[Wu, W., Vanderwall, D. E., Lui, S. M., Tang, X.-J., Turner, C. J., Kozarich, J. W., & Stubbe, J. (1996) J. Am. Chem. Soc. 118, 1268 - 1280]表明，这两种金属博来霉素具有相似的结构。糖质子的化学位移以及T1值表明，这些片段在Fe（II）BLM中与金属接近但未结合。
