Voznesensky A I, Galanova J V, Shkrob A M, Mathanov I E, Archakov A I
2nd Moscow Medical Institute, USSR.
Arch Biochem Biophys. 1990 Dec;283(2):519-22. doi: 10.1016/0003-9861(90)90676-p.
Hybrid molecules consisting of an address peptide and an active oxygen-generating fragment may be used for selective destruction of cells. We tested the possibility of using the antibiotic bleomycin (BLM) as an active oxygen-generating fragment of such a molecule. It was found that bleomycin can induce destruction of cell membranes. BLM-mediated cell destruction was inhibited by addition of catalase, superoxide dismutase, and OH. scavangers (mannitol and ethanol), suggesting that hydroxy radical is involved in the process. BLM can induce membrane impairment at the expense of electrons supplied by NADPH-cytochrome P450 reductase. Covalent binding of BLM to an address fragment (concanavalin A, immunoglobulin G) increases the ability of BLM to destroy erythrocyte membranes. The data obtained lead to the conclusion that BLM can be used as an active oxygen-generating fragment of a proposed cell-destroying hybrid molecule.
由地址肽和活性氧生成片段组成的杂合分子可用于选择性破坏细胞。我们测试了使用抗生素博来霉素(BLM)作为此类分子活性氧生成片段的可能性。发现博来霉素可诱导细胞膜破坏。添加过氧化氢酶、超氧化物歧化酶和羟基清除剂(甘露醇和乙醇)可抑制博来霉素介导的细胞破坏,这表明羟基自由基参与了该过程。博来霉素可通过消耗烟酰胺腺嘌呤二核苷酸磷酸-细胞色素P450还原酶提供的电子来诱导膜损伤。博来霉素与地址片段(伴刀豆球蛋白A、免疫球蛋白G)的共价结合增加了博来霉素破坏红细胞膜的能力。所得数据得出结论,博来霉素可作为所提出的细胞破坏杂合分子的活性氧生成片段。