Alcohols induce beta-hematin formation via the dissociation of aggregated heme and reduction in interfacial tension of the solution
Alcohols induce beta-hematin formation via the dissociation of aggregated heme and reduction in interfacial tension of the solution
复制标题
DOI：
10.1016/j.actatropica.2007.01.001
复制
发表时间：
2007-02-01
期刊：
影响因子：
2.7
通讯作者：
Kamei, Kaeko
中科院分区：
文献类型：
--
作者：
Huy, Nguyen T.;Maeda, Atsushi;Kamei, Kaeko
疟疾色素是一种独特的疟原虫色素晶体，其晶胞由血红素二聚体组成，其形成已被提议作为抗疟疾筛选的理想目标。 β-血红素（一种结构与疟原虫色素相同的合成晶体）形成机制表明，需要疏水相互作用来溶解血红素，但这一假设需要进一步的证据。直接研究疟疾食物泡中疟原虫色素的形成过程。由于脂质和蛋白质的复杂性，尚未进行。为了克服这一困难并探索β-血红素形成的环境条件，我们系统地研究了一系列结构相似的小正构醇（甲醇、乙醇、正丙醇和正丁醇）诱导β-血红素的形成。首次可以通过将血红素结晶增强 50%（EC50 值）所需的浓度来评估 β-血红素诱导剂的能力。这些值提供了一种快速、方便的工具来比较引发剂形成 β-血红素的能力。我们的结果表明，醇类诱导β-血红素形成的能力顺序为：正丁醇>正丙醇>乙醇>甲醇。醇诱导β-血红素形成与其疏水性程度和溶解血红素的能力有关，这表明醇对聚集血红素的解离是β-血红素形成的主要因素。此外，醇可以降低溶液的表面张力，从而降低产生临界核的能垒。 (c) 2007 Elsevier B.V. 保留所有权利。
The formation of the malarial pigment, a unique hemozoin crystal with unit cells comprised of heme dimers, has been proposed as an ideal target for antimalarial screening. The mechanism of beta-hematin formation (a synthetic crystal structurally identical to hemozoin) has been suggested that a hydrophobic interaction is needed to solubilize heme, but this hypothesis needs further evidence. Direct study of the process of hemozoin formation in the malarial food vacuole. has not been performed, due to complicated groups of lipids and proteins. To overcome this difficulty and to explore the environmental conditions for beta-hematin formation, we systematically studied beta-hematin formation induced by a series of small normal alcohols (methanol, ethanol, n-propanol, and n-butanol), which are structurally similar. For the first time, the ability of beta-hematin inducer could be evaluated by its concentration that is required to enhance heme crystallization by 50% (EC50 values). These values provide a rapid and convenient tool for comparing the ability of initiators in beta-hematin formation. Our results showed that the ability of alcohols to induce beta-hematin formation in the order: n-butanol > n-propanol > ethanol > methanol. The induction of beta-hematin formation by alcohols is related with their degree of hydrophobicity and ability to solubilize heme, suggesting that the dissociation of aggregated heme by alcohols is a major factor in beta-hematin formation. In addition, alcohols can reduce the surface tension of a solution, thus lowering the energy barrier for creating critical nuclei. (c) 2007 Elsevier B.V. All rights reserved.