博来霉素在体外导致DNA断裂的机制。
The mechanism of DNA breakage by phleomycin in vitro.
作者信息
Sleigh M J
出版信息
Nucleic Acids Res. 1976 Apr;3(4):891-901. doi: 10.1093/nar/3.4.891.
Abstract
Phleomycin induces DNA breakage in vitro in the presence of the sulphydryl compound dithiothreitol. The reaction appears to be free radical-mediated, and requires oxygen and metal ions. Reaction rate is limited by the concentration of oxygen, which is converted to hydrogen peroxide during DNA breakage. However there is no net change in the sulphydryl compound. The proposed reaction mechanism involves metal ion/oxygen-catalysed oxidation of dithiothreitol to its free radical form, which reacts with phleomycin, leading to formation of activated phleomycin and regeneration of free sulphydryl. Free phleomycin is converted to an inactive form, but activation of phleomycin bound to DNA leads to DNA breakage.
摘要
在巯基化合物二硫苏糖醇存在的情况下，博来霉素在体外可诱导DNA断裂。该反应似乎是由自由基介导的，并且需要氧气和金属离子。反应速率受氧气浓度的限制，在DNA断裂过程中氧气被转化为过氧化氢。然而，巯基化合物没有净变化。提出的反应机制涉及金属离子/氧气催化二硫苏糖醇氧化为其自由基形式，该自由基形式与博来霉素反应，导致活化博来霉素的形成和游离巯基的再生。游离博来霉素转化为无活性形式，但与DNA结合的博来霉素的活化会导致DNA断裂。
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