INTERACTIONS OF MODIFIED HEMOGLOBINS WITH IRON CHELATORS

在目前旨在减少苯系物氧化作用的策略中 HBOCs是使用铁络合剂来防止潜在的分子和 铁引起的氧自由基对细胞的损伤。我们学习了 去铁胺与一种新开发的药物相互作用的影响 吡喃酮、乙基麦芽酚对自氧化和过氧化氢速率的影响 交联型血红蛋白的介导氧化。有一点微不足道 自氧化和半铬形成的速度都会降低 含有这些血红蛋白的溶液中含有乙基麦芽酚。 相反，包含去铁胺会导致氧化增加。 产品。在反应混合物中和在过剩氢的存在下 过氧化氢，去铁胺导致高铁血红蛋白增加20-30% 半铬层的形成略有减少。乙基麦芽酚，在 另一方面，收效甚微或毫无效果。与乙基麦芽酚不同的是， 去铁胺，独立于它的螯合特性，作为一种 氧化剂。这可能与它的直接交互能力有关 氧自由基导致高铁血红蛋白生成增加。这个 观察到交联剂敏感性的相对差异 血红蛋白对去铁胺的促氧化活性可能反映了 蛋白质中血红素口袋的立体化学差异 由不同形式的化学修饰带来的。进一步研究 计划验证这一点并研究潜在的分子 去铁胺的作用机制。还计划进行一项后续研究 其中一种更强大和有效的铁络合吡啶酮家族 将使用化合物。

Among the current strategies aimed at decreasing the oxidant effect of HBOCs is the use of iron chelators to prevent the potential molecular and cellular damage caused by iron induced oxygen free radicals. We studied the effects of interactions of desferrioxamine and a newly developed pyrone, ethyl maltol, on the rate of autoxidation and hydrogen peroxide mediated oxidation of cross-linked hemoglobins. There was a slight decrease in both the rate of autoxidation and hemichrome formation when ethyl maltol was included in the solutions containing these hemoglobins. Conversely, inclusion of desferrioxamine led to an increase in oxidation products. In the reaction mixture and in the presence of excess hydrogen peroxide, desferrioxamine led to a 20-30 % rise in methemoglobin coupled with a slight reduction in the hemichrome formation. Ethyl maltol, on the other hand, has little or no effect. It appears that unlike ethyl maltol, desferrioxamine, independent of its chelating properties, acts as an oxidizing agent. This may relate to its ability to interact directly with oxygen free radicals resulting in increased methemoglobin formation. The observed relative differences in the susceptibility of cross-linked hemoglobins to the prooxidant activity of desferroxamine may reflect the differences in the stereochemistry of the heme pocket of the proteins brought about by different forms of chemical modification. Further studies are planned to verify this and to investigate the underlying molecular mechanism of desferrioxamine's action. Also planned is a follow up study in which a more powerful and effective family of iron chelating pyridinone compounds will be used.