キャピラリー電気泳動法による薬物の疎水性・酸解離定数及びタンパク質のアンフォールディングの評価に関する研究

概要

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Capillary electrophoresis (CE) was used to evaluate drug hydrophobicity, dissociation constants (pK_a), and protein unfolding. In one study, the hydrophobicity of solutes was measured by microemulsion electrokinetic chromatography (MEEKC). The logarithm of the capacity factors was highly correlated with the logarithm of the octanol/water partition coefficients (log P_<ow>). The reproducibility was drastically improved by using the migration index (MI). MI provided a better correlation with some bioactivites than did other hydrophobicity parameters, such as log P_<ow>. In a second study, a general equation for use in calculating pK_as from solute mobilities observed at different pHs was derived to be suitable for multivalent compounds with close pK_as. This method was useful for slightly soluble compounds and compounds containing some impurities or that decompose easily. In a third study, the thermodynamic parameters of the thermally-induced unfolding of proteins were determined by CE using an in-column incubation method. Although the apparent transition temperatures by CE were generally consistent with those obtained by far-UV CD, these two methods had different detection selectivities for changes in the protein structures. These nanoscale methods have some advantages, such as high speed and high reproducibility, and should be applicable in various fields.
社団法人日本分析化学会の論文
1999-08-05