Proton nuclear magnetic resonance study of the structure of bleomycin and the zinc-bleomycin complex.
Proton nuclear magnetic resonance study of the structure of bleomycin and the zinc-bleomycin complex.
复制标题
博莱霉素和锌-博莱霉素复合物结构的质子核磁共振研究。
DOI：
10.1021/bi00583a001
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发表时间：
1979
期刊：
影响因子：
2.9
通讯作者：
S. Hecht
中科院分区：
文献类型：
--
作者：
N. Oppenheimer;L. Rodriguez;S. Hecht
Norman J. Oppenheimer，* Luis O. Rodriguez，1和Sidney M. Hecht §摘要：在360 MHz下对博来霉素、改性博来霉素和锌-博来霉素复合物进行了1H NMR光谱研究。在这些研究中，博莱霉素的修正结构已经通过以下方式独立地验证：（1）化学位移的pD依赖性，（2）观察到与作为溶剂的（CD 3）2SO的可交换共振，和（3）β-氨基丙氨酸部分的α-胺的酰化。对博莱霉素锌配合物（D20为溶剂）的核磁共振谱进行了测定和分析。对于以下基团，在金属结合时观察到大于0.1 ppm的化学位移变化：（1）0-氨基丙氨酸，（2）丙酰胺，（3）嘧啶基甲基，（4）β-羟基组氨酸，（5）甘露糖3 '，和（6）戊酸甲酯。博莱霉素是一种糖肽类抗生素，与锌的配位作用也会引起邻位偶联常数的较大变化。（1966年）。它对鳞状细胞癌、各种淋巴瘤和睾丸癌显示出显著的选择性。特别重要的是免疫抑制的普遍缺乏（Boggs等人，1974），从而说明其在联合化疗中的使用增加。博来霉素的结构首先由Takita等人提出。（1972），以及Takita et al.（1978 a）见图1。该药物对二价过渡金属离子具有高亲和力，并以1：1铜配合物形式分离（Umezawa等人，1966; Umezawa，1974）。然而，亚铁-博来霉素复合物已被认为是博来霉素指导的DNA链断裂中可能的活性物质（Sausville等人，1976; Lown & Sim，1977）。
Norman J. Oppenheimer,* Luis O. Rodriguez, 1 and Sidney M. Hecht § abstract:* H NMR spectral studies at 360 MHz have been conducted on bleomycin, a modified bleomycin, and the zinc-bleomycin complex. In these studies, the revised structure of bleomycin has been independently verified by (1) the pD dependence of chemical shifts,(2) observation of the ex-changeable resonances with (CD3) 2SO as solvent, and (3) acylation of the «-amine of the/3-aminoalanine moiety. The NMR spectra of the zinc-bleomycin complex (D20 as solvent) have been obtained and analyzed. Chemical shift changes larger than 0.1 ppm are observed upon metal binding for the following groups:(1) 0-aminoalanine,(2) propionamide,(3) pyrimidinyl methyl,(4)/3-hydroxyhistidine,(5) mannose 3', and (6) methylvalerate. Coordination to zinc also causes large changes in vicinal coupling constants for theBleomycin is a glycopeptide antibioticfirst isolated from Streptomyces verticillus by Umezawa et al.(1966). It shows remarkable selectivity toward squamous cell carcinoma, various lymphomas, and testicular carcinoma. Of particular im-portance is the general absence of immunosuppression (Boggs et al., 1974), thus accountingfor itsincreased use in com-bination chemotherapy. The structure of bleomycin was first proposed by Takita et al.(1972), and a revised structure suggested by Takita et al.(1978a) is shown in Figure 1. The drug has a high affinity for divalent transition-metal ions and is isolated as the 1: 1 cupric complex (Umezawa et al., 1966; Umezawa, 1974). It is the ferrous-bleomycin complex, however, that has been implicated as the possible active species in bleomycin-directed DNA strand scission (Sausville et al., 1976; Lown & Sim, 1977).